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Mohamed I, Abosheiashaa H, Boda A, Yang F, Kamali E, Scott R, Huntress K, Saravanan T, Saelm AE, Jaber F, Abboud Y, Dahiya D, Alba L, Duong N. A systematic review and meta-analysis assessing the safety and efficacy of the hepatitis E virus vaccine. Proc AMIA Symp 2025; 38:327-333. [PMID: 40291089 PMCID: PMC12026039 DOI: 10.1080/08998280.2025.2474893] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 02/18/2025] [Accepted: 02/24/2025] [Indexed: 04/30/2025] Open
Abstract
Background Hepatitis E virus (HEV) is a global cause of viral hepatitis. While genotypes 1 and 2 cause acute hepatitis in Asia and Africa, genotypes 3 and 4 lead to sporadic acute or chronic hepatitis in America and Europe. Pregnant women, immunosuppressed individuals, and those with chronic liver disease face a higher risk of severe outcomes. HEV recombinant vaccine is approved for outbreak use in China but awaits Food and Drug Administration approval in the USA. This systematic review and meta-analysis aims to assess the safety and efficacy of the HEV vaccine. Methods We conducted a systematic search in Medline, Cochrane, Scopus, and Embase, employing specific terms for the recombinant HEV vaccine. Eligibility criteria involved all-age individuals receiving recombinant HEV vaccine in randomized controlled trials. Covidence software was used to screen studies, and data extraction encompassed study characteristics, baseline data, and efficacy outcomes by four reviewers. Bias evaluation was completed using Cochrane's RoB 2 tool. Statistical analysis involved use of Revman v5.4 with a random effect model, considering P < 0.05 as statistically significant. Heterogeneity was assessed using the I 2 test. Results The analysis revealed a statistically significant difference in HEV vaccine efficacy compared to placebo (odds ratio [OR]: 25.16, 95% confidence interval [CI] 9.21, 68.75, P < 0.00001) with a substantial reduction in hepatitis E cases (OR: 0.04, 95% CI 0.01, 0.11, P < 0.00001). In terms of safety, the HEV vaccine exhibited a significant increase in injection pain (OR: 1.56, 95% CI 1.03, 2.36, P = 0.04) and injection bruising (OR: 3.62, 95% CI 1.76, 7.48, P = 0.0005). No statistically significant differences were observed in fever (OR: 1.03, 95% CI 0.86, 1.23, P = 0.76) or headache (OR: 1.15, 95% CI 0.72, 1.84, P = 0.56). Local events significantly increased with the vaccine (OR: 1.50, 95% CI 1.38, 1.63, P < 0.00001). There were no significant differences in systemic events (OR: 1.06, 95% CI 0.86, 1.31, P = 0.59) or serious adverse events (OR: 0.58, 95% CI 0.16, 2.07, P = 0.40). Conclusion Our systematic review and meta-analysis demonstrates the significant and favorable impact of the recombinant HEV vaccine on the reduction of HEV cases. However, safety considerations are notable, as the vaccine is associated with a significant increase in injection-related pain and bruising. While localized adverse events were more frequent with the vaccine, there were no statistically significant differences in systemic events, serious adverse events, fever, or headache compared to placebo. These findings emphasize the overall effectiveness of the HEV vaccine in preventing HEV infections but highlight the need for careful monitoring and consideration of potential localized side effects.
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Affiliation(s)
- Islam Mohamed
- Department of Internal Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Hazem Abosheiashaa
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Anna Boda
- School of Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Felix Yang
- School of Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Emily Kamali
- School of Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Regina Scott
- School of Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Kate Huntress
- School of Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Tejas Saravanan
- School of Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Ahmed E. Saelm
- Department of Internal Medicine, Maimonides Medical Center, Brooklyn, New York, USA
| | - Fouad Jaber
- Department of Internal Medicine, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Yazan Abboud
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Dushyant Dahiya
- Division of Gastroenterology, Hepatology, and Motility, Kansas University, Kansas City, Kansas, USA
| | - Laura Alba
- Department of Gastroenterology and Hepatology, University of Missouri – Kansas City, Kansas City, Missouri, USA
| | - Nikki Duong
- Department of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA
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Grigas J, Spancerniene U, Simanavicius M, Pautienius A, Stankevicius R, Tamosiunas PL, Stankevicius A. Adaptive immune response to a wild boar-derived recombinant hepatitis e virus capsid protein challenge in pigs. Vaccine 2025; 44:126561. [PMID: 39617676 DOI: 10.1016/j.vaccine.2024.126561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/20/2024] [Accepted: 11/23/2024] [Indexed: 12/20/2024]
Abstract
Hepatitis E virus genotype 3 (HEV-3) is a zoonotic pathogen capable of infecting human, porcine, and other animal hosts. Despite a broad host range and abundance of species that act as reservoirs for human infections, no commercially available animal vaccines against HEV-3 are currently available. In the present study, we tested the capacity of recombinant aa 112-608 wild boar-derived HEV-3 capsid protein (rORF2p) to induce an immune response in immunized pigs. Four 6 week old pigs were administered 1 ml of 200 μg/ml rORF2p, followed by booster administration after 14 days. Blood samples were collected until 28 days after initial immunization. Dominant cell phenotypes and anti-HEV IgG concentrations were determined. A significant anti-HEV IgG, monocyte/macrophage, B cell and T cell response has been detected in immunized pigs. In turn, our findings suggest the capacity of rORF2p to elicit an immune response in pigs, suggesting the potential for its use as a vaccine candidate.
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Affiliation(s)
- Juozas Grigas
- Faculty of Veterinary Medicine, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania; Faculty of Veterinary Medicine, Institute of Microbiology and Virology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania.
| | - Ugne Spancerniene
- Faculty of Veterinary Medicine, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania.
| | - Martynas Simanavicius
- Vilnius University Life Sciences Centre, Institute of Biotechnology, Sauletekio al. 7, Vilnius, Lithuania.
| | - Arnoldas Pautienius
- Faculty of Veterinary Medicine, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania; Faculty of Veterinary Medicine, Institute of Microbiology and Virology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania.
| | - Rolandas Stankevicius
- Department of Animal Breeding and Nutrition, Faculty of Animal Husbandry Technology, Lithuanian University of Health Sciences, Tilzes Str. 18, Kaunas, Lithuania.
| | - Paulius Lukas Tamosiunas
- Vilnius University Life Sciences Centre, Institute of Biotechnology, Sauletekio al. 7, Vilnius, Lithuania.
| | - Arunas Stankevicius
- Faculty of Veterinary Medicine, Department of Anatomy and Physiology, Lithuanian University of Health Sciences, Tilzes str. 18, Kaunas, Lithuania.
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Meng S, Miao A, Wu S, Du X, Gao F. Genetically modified chickens as bioreactors for protein-based drugs. Front Genome Ed 2025; 6:1522837. [PMID: 39845893 PMCID: PMC11753250 DOI: 10.3389/fgeed.2024.1522837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 12/18/2024] [Indexed: 01/24/2025] Open
Abstract
Protein drug production encompasses various methods, among which animal bioreactors are emerging as a transgenic system. Animal bioreactors have the potential to reduce production costs and increase efficiency, thereby producing recombinant proteins that are crucial for therapeutic applications. Various species, including goats, cattle, rabbits, and poultry, have been genetically engineered to serve as bioreactors. This review delves into the analysis and comparison of different expression systems for protein drug production, highlighting the advantages and limitations of microbial, yeast, plant cell, and mammalian cell expression systems. Additionally, the emerging significance of genetically modified chickens as a potential bioreactor system for producing protein-based drugs is highlighted. The avian bioreactor enables the expression of target genes in ovarian cells, resulting in the production of corresponding gene expression products in egg whites. This production method boasts advantages such as a short cycle, high production efficiency, low research costs, and the expression products being closer to their natural state and easier to purify. It demonstrates immense potential in production applications, scientific research, and sustainable development. The utilization of advanced gene editing technologies, such as CRISPR/Cas9, has revolutionized the precision and efficiency of generating genetically modified chickens. This has paved the way for enhanced production of recombinant therapeutic proteins with desired glycosylation patterns and reduced immunogenic responses.
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Affiliation(s)
- Shujuan Meng
- Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Aijun Miao
- Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
| | - Sen Wu
- Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, China
| | - Xuguang Du
- Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, China
| | - Fei Gao
- Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
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Kang S, Chung E, Hong C, Aziz AB, Kirkwood CD, Marks F. Raising the case of hepatitis E: Report from the 2nd international HEV symposium. Vaccine 2024; 42:126398. [PMID: 39357463 DOI: 10.1016/j.vaccine.2024.126398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 07/02/2024] [Accepted: 09/24/2024] [Indexed: 10/04/2024]
Abstract
The 2nd International Hepatitis E Virus Symposium was held on April 28 and 29, 2023, in London, UK. The conference was hosted by the International Vaccine Institute and brought together key clinicians, researchers, and private and public stakeholders for a dedicated forum on hepatitis E virus (HEV). The scientific program spanned multiple facets of HEV, from updates on clinical research and diagnostic advances to vaccine development. The conference highlighted presentations on several critical HEV vaccine studies that will greatly impact the field, including the largest effectiveness study of Hecolin vaccine outside of China and the first reactive mass-vaccination campaign in South Sudan. This report summarizes information shared at the convening and offers perspectives on the steps forward for hepatitis E.
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Affiliation(s)
- Sophie Kang
- Epidemiology, Public Health and Impact, International Vaccine Institute, Seoul, South Korea.
| | - Eun Chung
- Epidemiology, Public Health and Impact, International Vaccine Institute, Seoul, South Korea
| | - Chloe Hong
- Epidemiology, Public Health and Impact, International Vaccine Institute, Seoul, South Korea
| | - Asma Binte Aziz
- Epidemiology, Public Health and Impact, International Vaccine Institute, Seoul, South Korea
| | - Carl D Kirkwood
- Enteric & Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation, Seattle, WA, USA
| | - Florian Marks
- Epidemiology, Public Health and Impact, International Vaccine Institute, Seoul, South Korea; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK; Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany; Madagascar Institute for Vaccine Research, University of Antananarivo, Antananarivo, Madagascar
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Sookhoo JRV, Schiffman Z, Ambagala A, Kobasa D, Pardee K, Babiuk S. Protein Expression Platforms and the Challenges of Viral Antigen Production. Vaccines (Basel) 2024; 12:1344. [PMID: 39772006 PMCID: PMC11680109 DOI: 10.3390/vaccines12121344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 11/19/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025] Open
Abstract
Several protein expression platforms exist for a wide variety of biopharmaceutical needs. A substantial proportion of research and development into protein expression platforms and their optimization since the mid-1900s is a result of the production of viral antigens for use in subunit vaccine research. This review discusses the seven most popular forms of expression systems used in the past decade-bacterial, insect, mammalian, yeast, algal, plant and cell-free systems-in terms of advantages, uses and limitations for viral antigen production in the context of subunit vaccine research. Post-translational modifications, immunogenicity, efficacy, complexity, scalability and the cost of production are major points discussed. Examples of licenced and experimental vaccines are included along with images which summarize the processes involved.
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Affiliation(s)
- Jamie R. V. Sookhoo
- Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, Winnipeg, MB R3E 3R2, Canada; (J.R.V.S.); (A.A.)
- Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
| | - Zachary Schiffman
- Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; (Z.S.); (D.K.)
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
| | - Aruna Ambagala
- Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, Winnipeg, MB R3E 3R2, Canada; (J.R.V.S.); (A.A.)
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
| | - Darwyn Kobasa
- Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; (Z.S.); (D.K.)
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
| | - Keith Pardee
- Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada;
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada
| | - Shawn Babiuk
- Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, Winnipeg, MB R3E 3R2, Canada; (J.R.V.S.); (A.A.)
- Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
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Tang S, Zhao C, Zhu X. Engineering Escherichia coli-Derived Nanoparticles for Vaccine Development. Vaccines (Basel) 2024; 12:1287. [PMID: 39591189 PMCID: PMC11598912 DOI: 10.3390/vaccines12111287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/13/2024] [Accepted: 11/13/2024] [Indexed: 11/28/2024] Open
Abstract
The development of effective vaccines necessitates a delicate balance between maximizing immunogenicity and minimizing safety concerns. Subunit vaccines, while generally considered safe, often fail to elicit robust and durable immune responses. Nanotechnology presents a promising approach to address this dilemma, enabling subunit antigens to mimic critical aspects of native pathogens, such as nanoscale dimensions, geometry, and highly repetitive antigen display. Various expression systems, including Escherichia coli (E. coli), yeast, baculovirus/insect cells, and Chinese hamster ovary (CHO) cells, have been explored for the production of nanoparticle vaccines. Among these, E. coli stands out due to its cost-effectiveness, scalability, rapid production cycle, and high yields. However, the E. coli manufacturing platform faces challenges related to its unfavorable redox environment for disulfide bond formation, lack of post-translational modifications, and difficulties in achieving proper protein folding. This review focuses on molecular and protein engineering strategies to enhance protein solubility in E. coli and facilitate the in vitro reassembly of virus-like particles (VLPs). We also discuss approaches for antigen display on nanocarrier surfaces and methods to stabilize these carriers. These bioengineering approaches, in combination with advanced nanocarrier design, hold significant potential for developing highly effective and affordable E. coli-derived nanovaccines, paving the way for improved protection against a wide range of infectious diseases.
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Affiliation(s)
- Shubing Tang
- Shanghai Reinovax Biologics Co., Ltd., Pudong New District, Shanghai 200135, China;
| | - Chen Zhao
- Shanghai Public Health Clinical Center, Fudan University, Shanghai 201058, China
| | - Xianchao Zhu
- Shanghai Reinovax Biologics Co., Ltd., Pudong New District, Shanghai 200135, China;
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Guo H, Xu J, Situ J, Li C, Wang X, Hou Y, Yang G, Wang L, Ying D, Li Z, Wang Z, Su J, Ding Y, Zeng D, Zhang J, Ding X, Wu S, Miao W, Tang R, Lu Y, Kong H, Zhou P, Zheng Z, Zheng K, Pan X, Sridhar S, Wang W. Cell binding tropism of rat hepatitis E virus is a pivotal determinant of its zoonotic transmission to humans. Proc Natl Acad Sci U S A 2024; 121:e2416255121. [PMID: 39467126 PMCID: PMC11551445 DOI: 10.1073/pnas.2416255121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 09/09/2024] [Indexed: 10/30/2024] Open
Abstract
Classically, all hepatitis E virus (HEV) variants causing human infection belong to the genus Paslahepevirus (HEV-A). However, the increasing cases of rat HEV infection in humans since 2018 challenged this dogma, posing increasing health threats. Herein, we investigated the underlying mechanisms dictating the zoonotic potentials of different HEV species and their possible cross-protection relationships. We found that rat HEV virus-like particles (HEVVLPs) bound to human liver and intestinal cells/tissues with high efficiency. Moreover, rat HEVVLPs and infectious rat HEV particles penetrated the cell membrane and entered human target cells postbinding. In contrast, ferret HEVVLPs showed marginal cell binding and entry ability, bat HEVVLPs and avian HEVVLPs exhibited no binding and entry potency. Structure-based three-dimensional mapping identified that the surface spike domain of rat HEV is crucial for cell binding. Antigenic cartography indicated that rat HEV exhibited partial cross-reaction with HEV-A. Intriguingly, sera of HEV-A infected patients or human HEV vaccine Hecolin® immunized individuals provided partial cross-protection against the binding of rat HEVVLPs to human target cells. In summary, the interactions between the viral capsid and cellular receptor(s) regulate the distinct zoonotic potentials of different HEV species. The systematic characterization of antigenic cartography and serological cross-reactivity of different HEV species provide valuable insights for the development of species-specific diagnosis and protective vaccines against zoonotic HEV infection.
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Affiliation(s)
- Hongbo Guo
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Jiaqi Xu
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Jianwen Situ
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Chunyang Li
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Xia Wang
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou221002, China
| | - Yao Hou
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Guangde Yang
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou221002, China
| | - Lingli Wang
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Dong Ying
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen361102, China
| | - Zheng Li
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Zijie Wang
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Jia Su
- Chinese Academy of Sciences Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan430207, China
- Guangzhou Laboratory, Guangzhou International Bio Island, Guangzhou510320, China
| | - Yibo Ding
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Dou Zeng
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Jikai Zhang
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Xiaohui Ding
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Shusheng Wu
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Weiwei Miao
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Renxian Tang
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Yihan Lu
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai200032, China
| | - Huihui Kong
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin150069, China
| | - Peng Zhou
- Guangzhou Laboratory, Guangzhou International Bio Island, Guangzhou510320, China
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen361102, China
| | - Kuiyang Zheng
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
| | - Xiucheng Pan
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou221002, China
| | - Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Wenshi Wang
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou221004, China
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Al Beloushi M, Saleh H, Ahmed B, Konje JC. Congenital and Perinatal Viral Infections: Consequences for the Mother and Fetus. Viruses 2024; 16:1698. [PMID: 39599813 PMCID: PMC11599085 DOI: 10.3390/v16111698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 10/13/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024] Open
Abstract
Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.
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Affiliation(s)
- Mariam Al Beloushi
- Women’s Wellness and Research Centre Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.B.); (H.S.)
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Huda Saleh
- Women’s Wellness and Research Centre Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.B.); (H.S.)
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Badreldeen Ahmed
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
- Feto Maternal Centre, Al Markhiya Doha, Doha P.O. Box 34181, Qatar
- Department of Obstetrics and Gynaecology Weill Cornell Medicine, Doha P.O. Box 24144, Qatar
| | - Justin C. Konje
- Feto Maternal Centre, Al Markhiya Doha, Doha P.O. Box 34181, Qatar
- Department of Obstetrics and Gynaecology Weill Cornell Medicine, Doha P.O. Box 24144, Qatar
- Department of Health Sciences, University of Leicester, P.O. Box 7717, Leicester LE2 7LX, UK
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Kobayashi T, Takahashi M, Ohta S, Hoshino Y, Yamada K, Jirintai S, Primadharsini PP, Nagashima S, Murata K, Okamoto H. Production and Characterization of Self-Assembled Virus-like Particles Comprising Capsid Proteins from Genotypes 3 and 4 Hepatitis E Virus (HEV) and Rabbit HEV Expressed in Escherichia coli. Viruses 2024; 16:1400. [PMID: 39339876 PMCID: PMC11437457 DOI: 10.3390/v16091400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 08/28/2024] [Accepted: 08/29/2024] [Indexed: 09/30/2024] Open
Abstract
The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli. We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7-95.3%), as assessed by bioanalyzer, with yields of 13.9-89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development.
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Affiliation(s)
- Tominari Kobayashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Satoshi Ohta
- Division of Structural Biochemistry, Department of Biochemistry, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan;
| | - Yu Hoshino
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Kentaro Yamada
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Suljid Jirintai
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Putu Prathiwi Primadharsini
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Kazumoto Murata
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Tochigi, Japan; (T.K.); (M.T.); (P.P.P.); (S.N.); (K.M.)
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10
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Hartley C, Wasuwanich P, Van T, Karnsakul W. Hepatitis E Vaccines Updates. Vaccines (Basel) 2024; 12:722. [PMID: 39066361 PMCID: PMC11281573 DOI: 10.3390/vaccines12070722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 06/13/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024] Open
Abstract
The development of a hepatitis E vaccine is imperative given its prevalence and the heightened risk it poses to specific populations. Hepatitis E virus infection, though often self-limiting, poses a significant threat to pregnant individuals and immunocompromised populations. This review delves into the historical trajectory of hepatitis E vaccine development and explores its potential impact on at-risk populations. Historically, efforts to formulate an effective vaccine against hepatitis E have been underway to mitigate the severity of the disease, particularly in regions where the infection is commonplace. As a self-limiting disease, the necessity of a vaccine becomes more pronounced when considering vulnerable demographics. Pregnant individuals face heightened complications, with potential adverse outcomes for both mother and child. Similarly, immunocompromised individuals experience prolonged and severe manifestations of the infection, necessitating targeted preventive measures. This review aims to provide a comprehensive overview of the milestones in hepatitis E vaccine development. By examining the historical progression, we aim to underscore the critical need for a vaccine to safeguard not only the general population but also those at elevated risk. The elucidation of the vaccine's journey will contribute valuable insights into its potential benefits, aiding in the formulation of informed public health strategies to combat hepatitis E effectively.
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Affiliation(s)
- Christopher Hartley
- The Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA
| | - Paul Wasuwanich
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Trung Van
- Department of Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA;
| | - Wikrom Karnsakul
- Pediatric Liver Center, The Department of Pediatrics, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
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11
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Lu Q, Wu H, Meng J, Wang J, Wu J, Liu S, Tong J, Nie J, Huang W. Multi-epitope vaccine design for hepatitis E virus based on protein ORF2 and ORF3. Front Microbiol 2024; 15:1372069. [PMID: 38577684 PMCID: PMC10991829 DOI: 10.3389/fmicb.2024.1372069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 03/07/2024] [Indexed: 04/06/2024] Open
Abstract
Introduction Hepatitis E virus (HEV), with heightened virulence in immunocompromised individuals and pregnant women, is a pervasive threat in developing countries. A globaly available vaccine against HEV is currently lacking. Methods We designed a multi-epitope vaccine based on protein ORF2 and ORF3 of HEV using immunoinformatics. Results The vaccine comprised 23 nontoxic, nonallergenic, soluble peptides. The stability of the docked peptide vaccine-TLR3 complex was validated by molecular dynamic simulations. The induction of effective cellular and humoral immune responses by the multi-peptide vaccine was verified by simulated immunization. Discussion These findings provide a foundation for future HEV vaccine studies.
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Affiliation(s)
- Qiong Lu
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
| | - Hao Wu
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
- Wuhan Institute of Biological Products Co., Ltd., Wuhan, China
| | - Jing Meng
- State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, Jiangsu, China
| | | | - Jiajing Wu
- Research and Development Department, Beijing Yunling Biotechnology Co., Ltd., Beijing, China
| | - Shuo Liu
- Changping Laboratory, Beijing, China
- Graduate School of Peking Union Medical College, Beijing, China
| | - Jincheng Tong
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
| | - Jianhui Nie
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
| | - Weijin Huang
- Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
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12
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Kato H. Cost-effectiveness of hepatitis E virus vaccination strategy. Hepatol Res 2024; 54:122-124. [PMID: 38091250 DOI: 10.1111/hepr.14000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2023]
Affiliation(s)
- Hideaki Kato
- Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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13
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Vento S, Cainelli F. Acute liver failure in low-income and middle-income countries. Lancet Gastroenterol Hepatol 2023; 8:1035-1045. [PMID: 37837969 DOI: 10.1016/s2468-1253(23)00142-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/28/2023] [Accepted: 05/03/2023] [Indexed: 10/16/2023]
Abstract
Acute liver failure is a rare condition involving the rapid development, progression, and worsening of liver dysfunction, characterised by coagulopathy and encephalopathy, and has a high mortality unless liver transplantation is performed. Population-based studies are scarce, and most published data are from high-income countries, where the main cause of acute liver failure is paracetamol overdose. This Review provides an overview of the scanty literature on acute liver failure in low-income and middle-income countries, where patients are often admitted to primary care hospitals and viral hepatitis (especially hepatitis E), tropical infections (eg, dengue), traditional medicines, and drugs (especially anti-tuberculosis drugs) have an important role. We discuss incidence, cause, occurrence in children and pregnant women, prognostic factors and scores, treatment, and mortality. To conclude, we advocate for international collaboration, the establishment of central registries for the condition, and better diagnostics.
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Affiliation(s)
- Sandro Vento
- Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia.
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14
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Peron JM, Larrue H, Izopet J, Buti M. The pressing need for a global HEV vaccine. J Hepatol 2023; 79:876-880. [PMID: 37003442 DOI: 10.1016/j.jhep.2023.03.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 02/15/2023] [Accepted: 03/21/2023] [Indexed: 04/03/2023]
Abstract
Based on the worldwide distribution of hepatitis E virus (HEV) and its ability to cause major epidemics in low-income countries, the global availability of a HEV vaccine is a pressing clinical need. Populations at risk of severe forms of the infection are well characterised: patients with chronic liver disease - at risk of liver failure; pregnant women - at risk of fulminant hepatitis or obstetrical complications; and immunosuppressed patients, particularly those with solid organ transplants - at risk of chronic hepatitis and rapid progression to cirrhosis. Only one hepatitis E vaccine is presently being manufactured. It has been proven to be effective and safe. However, its accessibility, as well as data on its long-term efficacy and the duration of protection it confers, are limited. While individuals considered to be at risk of severe infection appear to be ideal targets for the vaccine, its effectiveness and tolerability have not yet been studied in populations with chronic liver disease and immunosuppressed patients. Hepatitis E vaccination could also play an important role in controlling outbreaks in large waterborne epidemics. Clinical trials on these populations are needed.
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Affiliation(s)
- Jean-Marie Peron
- Service d'Hépatologie, Hôpital Rangueil, CHU de Toulouse, Université Paul Sabatier Toulouse-III, France
| | - Hélène Larrue
- Service d'Hépatologie, Hôpital Rangueil, CHU de Toulouse, Université Paul Sabatier Toulouse-III, France
| | - Jacques Izopet
- CHU de Toulouse, Hôpital Purpan, Laboratoire de Virologie, Centre National de Référence du Virus de L'hépatite E, Toulouse, France
| | - Maria Buti
- Liver Unit, Hospital Universitario Valle Hebrón, CIBER del Instituto Carlos III, Barcelona, Spain.
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15
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Khuroo MS. Discovery of Hepatitis E and Its Impact on Global Health: A Journey of 44 Years about an Incredible Human-Interest Story. Viruses 2023; 15:1745. [PMID: 37632090 PMCID: PMC10459142 DOI: 10.3390/v15081745] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/09/2023] [Accepted: 08/10/2023] [Indexed: 08/27/2023] Open
Abstract
The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and pregnancy in developing countries and the opportunity for a massive epidemic of viral hepatitis, which hit the Gulmarg Kashmir region in November 1978. Based on data collected from a door-to-door survey, the existence of a new disease, epidemic non-A, non-B hepatitis, caused by a hitherto unknown hepatitis virus, was announced. This news was received by the world community with hype and skepticism. In the early 1980s, the world watched in awe as an extreme example of human self-experimentation led to the identification of VLP. In 1990, a cDNA clone from the virus responsible for epidemic non-A, non-B hepatitis was isolated. Over the years, we traversed three eras of ambiguity, hope, and hype of hepatitis E research and conducted several seminal studies to understand the biology of HEV and manifestations of hepatitis E. Many milestones have been reached on the long and winding road of hepatitis E research to understand the structure, biology, and diversity of the agent, changing the behavior of the pathogen in developed countries, and the discovery of a highly effective vaccine.
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Affiliation(s)
- Mohammad Sultan Khuroo
- Digestive Diseases Centre, Dr. Khuroo's Medical Clinic, Srinagar, Jammu & Kashmir 190010, India
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16
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Zahmanova G, Takova K, Tonova V, Koynarski T, Lukov LL, Minkov I, Pishmisheva M, Kotsev S, Tsachev I, Baymakova M, Andonov AP. The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development. Viruses 2023; 15:1558. [PMID: 37515244 PMCID: PMC10383931 DOI: 10.3390/v15071558] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
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Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Valeria Tonova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Tsvetoslav Koynarski
- Department of Animal Genetics, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Laura L Lukov
- Faculty of Sciences, Brigham Young University-Hawaii, Laie, HI 96762, USA
| | - Ivan Minkov
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Maria Pishmisheva
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Stanislav Kotsev
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
| | - Anton P Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
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17
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Cao YF, Zhou YF, Zhao DY, Chang JL, Tang JG, Chang DY, Zhang XM, Wang XP. Expression and immunogenicity of hepatitis E virus-like particles based on recombinant truncated ORF2 capsid protein. Protein Expr Purif 2023; 203:106214. [PMID: 36526214 DOI: 10.1016/j.pep.2022.106214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 12/10/2022] [Accepted: 12/13/2022] [Indexed: 12/15/2022]
Abstract
Hepatitis E is an emerging zoonotic disease, posing a severe threat to public health in the world. Since there are no specific treatments available for HEV infection, it is crucial to develop vaccine to prevent this infection. In this study, the truncated ORF2 encoded protein of 439aa∼617aa (HEV3-179) from HEV CCJD-517 isolates was expressed as VLPs in E. coli with diameters of approximate 20 nm. HEV3-179 protein was immunized with mice, and the results showed that a higher titre of antibody was induced in NIH mice in comparison with that of KM mice (P < 0.01) and BALB/c mice (P < 0.01). The induced antibody titer is much higher in subcutaneous immunization mice than that in the mice inoculated via abdominal immunization (P < 0.05) and muscles immunization (P < 0.01). Mice immunized with 12 μg and 6 μg candidate vaccine induced higher level of antibody titer than that of 3 μg dosage group (P < 0.01, P < 0.05). Antibody change curve showed that HEV IgG antibody titer increased from 14 days post immunization (dpi) to 1:262144 and reached the peak level on 42 dpi before gradually retreated with the same level antibody titer with 1:131072 until 84 dpi. Mice inoculated with HEV3-179 produced higher titer of cytokines than the mock group, and the concentration of IL-1β (P < 0.01) and IFN-γ (P < 0.01) further increased after stimulated by candidate vaccine. The result indicated that HEV3-179 possesses good immunogenicity, which could be used as a potential candidate for future HEV vaccine development.
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Affiliation(s)
- Yu-Feng Cao
- College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun, 130062, Jilin, China; Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China; Immune-Path Biotechnology (Suzhou) Co., Ltd, Suzhou, 215000, PR China
| | - Yong-Fei Zhou
- Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China; School of Life Sciences, Jilin University, Changchun, 130012, Jilin, China
| | - Dan-Ying Zhao
- Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China
| | - Jun-Liang Chang
- Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China
| | - Jian-Guang Tang
- Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China
| | - Dong-Ying Chang
- Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China
| | - Xue-Mei Zhang
- Changchun Institute of Biological Products Co. Ltd., 1616 Chuangxin Road, Changchun, 130012, Jilin, China.
| | - Xin-Ping Wang
- College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun, 130062, Jilin, China; Key Laboratory for Zoonosis, Ministry of Education, Institute for Zoonosis of Jilin University, Changchun, 130062, Jilin, China.
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18
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Elbahrawy A, Atalla H, Alboraie M, Alwassief A, Madian A, El Fayoumie M, Tabll AA, Aly HH. Recent Advances in Protective Vaccines against Hepatitis Viruses: A Narrative Review. Viruses 2023; 15:214. [PMID: 36680254 PMCID: PMC9862019 DOI: 10.3390/v15010214] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/03/2023] [Accepted: 01/07/2023] [Indexed: 01/15/2023] Open
Abstract
Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.
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Affiliation(s)
- Ashraf Elbahrawy
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Hassan Atalla
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mohamed Alboraie
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed Alwassief
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
- Gastroenterology Unit, Department of Internal Medicine, Sultan Qaboos University Hospital, P.O. Box 50, Muscat 123, Oman
| | - Ali Madian
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt
| | - Mohammed El Fayoumie
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Center, Giza 12622, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt
| | - Hussein H. Aly
- Department of Virology II, National Institute of Infectious Diseases, Toyama1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
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19
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Zhang J, Zheng Z, Xia N. Prophylactic Hepatitis E Vaccine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1417:227-245. [PMID: 37223870 DOI: 10.1007/978-981-99-1304-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
The hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals, two of them were tested in human and evidenced to be well-tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin® (HEV 239 vaccine), was licensed in China and launched in 2012.
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Affiliation(s)
- Jun Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
| | - Zizheng Zheng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
| | - Ningshao Xia
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China
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20
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Omics-guided bacterial engineering of Escherichia coli ER2566 for recombinant protein expression. Appl Microbiol Biotechnol 2023; 107:853-865. [PMID: 36539564 PMCID: PMC9767853 DOI: 10.1007/s00253-022-12339-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/07/2022] [Accepted: 12/10/2022] [Indexed: 12/24/2022]
Abstract
The goal of bacterial engineering is to rewire metabolic pathways to generate high-value molecules for various applications. However, the production of recombinant proteins is constrained by the complexity of the connections between cellular physiology and recombinant protein synthesis. Here, we used a rational and highly efficient approach to improve bacterial engineering. Based on the complete genome and annotation information of the Escherichia coli ER2566 strain, we compared the transcriptomic profiles of the strain under leaky expression and low temperature-induced stress. Combining the gene ontology (GO) enrichment terms and differentially expressed genes (DEGs) with higher expression, we selected and knocked out 36 genes to determine the potential impact of these genes on protein production. Deletion of bluF, cydA, mngR, and udp led to a significant decrease in soluble recombinant protein production. Moreover, at low-temperature induction, 4 DEGs (gntK, flgH, flgK, flgL) were associated with enhanced expression of the recombinant protein. Knocking out several motility-related DEGs (ER2666-ΔflgH-ΔflgL-ΔflgK) simultaneously improved the protein yield by 1.5-fold at 24 °C induction, and the recombinant strain had the potential to be applied in the expression studies of different exogenous proteins, aiming to improve the yields of soluble form to varying degrees in comparison to the ER2566 strain. Totally, this study focused on the anabolic and stress-responsive hub genes of the adaptation of E. coli to recombinant protein overexpression on the transcriptome level and constructs a series of engineering strains increasing the soluble protein yield of recombinant proteins which lays a solid foundation for the engineering of bacterial strains for recombinant technological advances. KEY POINTS: • Comparative transcriptome analysis shows host responses with altered induction stress. • Deletion of bluF, cydA, mngR, and udp genes was identified to significantly decrease the soluble recombinant protein productions. • Synchronal knockout of flagellar genes in E. coli can enhance recombinant protein yield up to ~ 1.5-fold at 24 °C induction. • Non-model bacterial strains can be re-engineered for recombinant protein expression.
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21
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Khanna D, Kar P. Can the diagnostics of hepatitis in pregnant patients be improved? Expert Rev Mol Diagn 2022; 22:1053-1055. [PMID: 36462167 DOI: 10.1080/14737159.2022.2153039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
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22
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Kayesh MEH, Kohara M, Tsukiyama-Kohara K. Epidemiology and Risk Factors for Acute Viral Hepatitis in Bangladesh: An Overview. Microorganisms 2022; 10:2266. [PMID: 36422336 PMCID: PMC9695917 DOI: 10.3390/microorganisms10112266] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 11/17/2022] Open
Abstract
Viral infections by hepatotropic viruses can cause both acute and chronic infections in the liver, resulting in morbidity and mortality in humans. Hepatotropic viruses, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV), are the major pathogens that cause acute and chronic infections in humans. Although all of these viruses can cause acute hepatitis in humans, HAV and HEV are the predominant causative agents in Bangladesh, where the occurrence is sporadic throughout the year. In this review, we provide an overview of the epidemiology of hepatotropic viruses that are responsible for acute hepatitis in Bangladesh. Additionally, we focus on the transmission modes of these viruses and the control and prevention of infections.
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Affiliation(s)
- Mohammad Enamul Hoque Kayesh
- Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal 8210, Bangladesh
| | - Michinori Kohara
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
| | - Kyoko Tsukiyama-Kohara
- Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan
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23
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Shata MTM, Hetta HF, Sharma Y, Sherman KE. Viral hepatitis in pregnancy. J Viral Hepat 2022; 29:844-861. [PMID: 35748741 PMCID: PMC9541692 DOI: 10.1111/jvh.13725] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/17/2021] [Accepted: 06/13/2022] [Indexed: 12/09/2022]
Abstract
Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.
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Affiliation(s)
- Mohamed Tarek M. Shata
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Helal F. Hetta
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA,Department of Medical Microbiology and Immunology, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Yeshika Sharma
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Kenneth E. Sherman
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
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24
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Warner JB, Guenthner SC, Hardesty JE, McClain CJ, Warner DR, Kirpich IA. Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease. World J Gastroenterol 2022; 28:5280-5299. [PMID: 36185629 PMCID: PMC9521517 DOI: 10.3748/wjg.v28.i36.5280] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/16/2022] [Accepted: 09/06/2022] [Indexed: 02/06/2023] Open
Abstract
Alcohol-associated liver disease (ALD) is a common chronic liver disease and major contributor to liver disease-related deaths worldwide. Despite its pre-valence, there are few effective pharmacological options for the severe stages of this disease. While much pre-clinical research attention is paid to drug development in ALD, many of these experimental therapeutics have limitations such as poor pharmacokinetics, poor efficacy, or off-target side effects due to systemic administration. One means of addressing these limitations is through liver-targeted drug delivery, which can be accomplished with different platforms including liposomes, polymeric nanoparticles, exosomes, bacteria, and adeno-associated viruses, among others. These platforms allow drugs to target the liver passively or actively, thereby reducing systemic circulation and increasing the ‘effective dose’ in the liver. While many studies, some clinical, have applied targeted delivery systems to other liver diseases such as viral hepatitis or hepatocellular carcinoma, only few have investigated their efficacy in ALD. This review provides basic information on these liver-targeting drug delivery platforms, including their benefits and limitations, and summarizes the current research efforts to apply them to the treatment of ALD in rodent models. We also discuss gaps in knowledge in the field, which when addressed, may help to increase the efficacy of novel therapies and better translate them to humans.
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Affiliation(s)
- Jeffrey Barr Warner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Steven Corrigan Guenthner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Josiah Everett Hardesty
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Craig James McClain
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Veterans Health Administration, Robley Rex Veterans Medical Center, Louisville, KY 40206, United States
| | - Dennis Ray Warner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Irina Andreyevna Kirpich
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, United States
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Lambidis E, Chen CC, Baikoghli M, Imlimthan S, Khng YC, Sarparanta M, Cheng RH, Airaksinen AJ. Development of 68Ga-Labeled Hepatitis E Virus Nanoparticles for Targeted Drug Delivery and Diagnostics with PET. Mol Pharm 2022; 19:2971-2979. [PMID: 35857429 PMCID: PMC9346612 DOI: 10.1021/acs.molpharmaceut.2c00359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
![]()
Targeted delivery of diagnostics and therapeutics offers
essential
advantages over nontargeted systemic delivery. These include the reduction
of toxicity, the ability to reach sites beyond biological barriers,
and the delivery of higher cargo concentrations to diseased sites.
Virus-like particles (VLPs) can efficiently be used for targeted delivery
purposes. VLPs are derived from the coat proteins of viral capsids.
They are self-assembled, biodegradable, and homogeneously distributed.
In this study, hepatitis E virus (HEV) VLP derivatives, hepatitis
E virus nanoparticles (HEVNPs), were radiolabeled with gallium-68,
and consequently, the biodistribution of the labeled [68Ga]Ga-DOTA-HEVNPs was studied in mice. The results indicated that
[68Ga]Ga-DOTA-HEVNPs can be considered as promising theranostic
nanocarriers, especially for hepatocyte-targeting therapies.
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Affiliation(s)
- Elisavet Lambidis
- Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki FI-00014, Finland
| | - Chun-Chieh Chen
- Department of Molecular and Cellular Biology, University of California, Davis, California 95616, United States
| | - Mo Baikoghli
- Department of Molecular and Cellular Biology, University of California, Davis, California 95616, United States
| | - Surachet Imlimthan
- Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki FI-00014, Finland
| | - You Cheng Khng
- Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki FI-00014, Finland
| | - Mirkka Sarparanta
- Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki FI-00014, Finland
| | - R Holland Cheng
- Department of Molecular and Cellular Biology, University of California, Davis, California 95616, United States
| | - Anu J Airaksinen
- Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki FI-00014, Finland.,Turku PET Centre, Department of Chemistry, University of Turku, Turku FI-20520, Finland
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Cross-Species Transmission of Rabbit Hepatitis E Virus to Pigs and Evaluation of the Protection of a Virus-like Particle Vaccine against Rabbit Hepatitis E Virus Infection in Pigs. Vaccines (Basel) 2022; 10:vaccines10071053. [PMID: 35891218 PMCID: PMC9320745 DOI: 10.3390/vaccines10071053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/21/2022] [Accepted: 06/26/2022] [Indexed: 11/28/2022] Open
Abstract
We investigated the cross-species transmission of rabbit hepatitis E virus (rb HEV) to pigs and evaluated the cross-protection of a swine (sw) HEV-3 virus-like particle (VLP) vaccine against rb HEV infection in pigs. Twelve 4-week-old conventional pigs were divided into negative control (n = 3), positive control (rb HEV-infected, n = 4), and vaccinated (vaccinated and rb HEV-challenged, n = 5) groups. The vaccine was administered at weeks 0 and 2, and viral challenge was conducted at week 4. Serum HEV RNA, anti-HEV antibody, cytokine, and liver enzyme levels were determined. Histopathological lesions were examined in abdominal organs. Viral RNA was detected and increased anti-HEV antibody and alanine aminotransferase (ALT) levels were observed in positive control pigs; liver fibrosis, inflammatory cell infiltration in the lamina propria of the small intestine and shortened small intestine villi were also observed. In vaccinated pigs, anti-HEV antibody and Th1 cytokine level elevations were observed after the second vaccination; viral RNA was not detected, and ALT level elevations were not observed. The results verified the cross-species transmission of rb HEV to pigs and cross-protection of the sw HEV-3 VLP vaccine against rb HEV infection in pigs. This vaccine may be used for cross-protection against HEV infection in other species.
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Serology versus nucleic acid amplification to diagnose acute hepatitis E, United Kingdom, 2014-18. J Infect 2022; 85:327-333. [PMID: 35753571 DOI: 10.1016/j.jinf.2022.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 06/16/2022] [Accepted: 06/17/2022] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Diagnosing hepatitis E infection usually involves specific IgM testing, but sensitivity/specificity concerns mean many guidelines and practices include confirmatory tests. We studied whether additional information confirmatory tests provide justifies their use. METHODS We examined 9,131 records of anti-hepatitis E IgM assays, 7,615 of IgG assays, and 1,726 of RT-PCR assays from our regional laboratory, spanning October 2014-October 2018. We paired 495 IgM assay results with a RT-PCR result. We examined whether IgM results predicted PCR results, reviewed discrepant pairs, and investigated the correlation between IgG and PCR results in patients with strongly reactive IgM assays. RESULTS Anti-hepatitis E IgM titres are bimodal. A high cut-off value optimises prediction of RNA detectability. 7/404 low-IgM samples had detectable RNA, 6 from immunosuppressed patients. 26/91 high-IgM samples did not have detectable RNA. In high-IgM samples, RNA detectability was not associated with IgG titre (one-tailed Mann-Whitney U test, p=0.14). CONCLUSIONS In immunocompetent patients, tests beyond IgM seldom add clinically useful information. In patients with immunocompromise, IgM and RNA could contribute information. Additional tests' extra costs/intervention delays cannot be justified. IgM assay cut-offs should reflect titres' bimodal distribution, with values standardised using international units.
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Dionne-Odom J, Cozzi GD, Franco RA, Njei B, Tita ATN. Treatment and prevention of viral hepatitis in pregnancy. Am J Obstet Gynecol 2022; 226:335-346. [PMID: 34516961 PMCID: PMC8907340 DOI: 10.1016/j.ajog.2021.09.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/03/2021] [Accepted: 09/07/2021] [Indexed: 02/06/2023]
Abstract
Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.
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Affiliation(s)
- Jodie Dionne-Odom
- Division of Infectious Diseases, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL; Center for Women's Reproductive Health, The University of Alabama at Birmingham, Birmingham, AL.
| | - Gabriella D Cozzi
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, AL
| | - Ricardo A Franco
- Division of Infectious Diseases, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL
| | - Basile Njei
- Yale Center for Clinical Investigation, Yale School of Medicine, New Haven, CT
| | - Alan T N Tita
- Center for Women's Reproductive Health, The University of Alabama at Birmingham, Birmingham, AL; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, AL
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Induction of Hepatitis E Virus Anti-ORF3 Antibodies from Systemic Administration of a Muscle-Specific Adeno-Associated Virus (AAV) Vector. Viruses 2022; 14:v14020266. [PMID: 35215859 PMCID: PMC8878420 DOI: 10.3390/v14020266] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/23/2022] [Accepted: 01/24/2022] [Indexed: 01/25/2023] Open
Abstract
The hepatitis E virus (HEV) is a major global health problem, leading to large outbreaks in the developing world and chronic infections in the developed world. HEV is a non-enveloped virus, which circulates in the blood in a quasi-enveloped form. The quasi-envelope protects HEV particles from neutralising anti-capsid antibodies in the serum; however, most vaccine approaches are designed to induce an immune response against the HEV capsid. In this study, we explored systemic in vivo administration of a novel synthetic and myotropic Adeno-associated virus vector (AAVMYO3) to express the small HEV phosphoprotein ORF3 (found on quasi-enveloped HEV) in the musculature of mice, resulting in the robust and dose-dependent formation of anti-ORF3 antibodies. Neutralisation assays using the serum of ORF3 AAV-transduced mice showed a modest inhibitory effect on the infection of quasi-enveloped HEV in vivo, comparable to previously characterised anti-ORF3 antibodies used as a control. The novel AAVMYO3 capsid used in this study can serve as a versatile platform for the continued development of vector-based vaccines against HEV and other infectious agents, which could complement traditional vaccines akin to the current positive experience with SARS-CoV-2.
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Cancela F, Noceti O, Arbiza J, Mirazo S. Structural aspects of hepatitis E virus. Arch Virol 2022; 167:2457-2481. [PMID: 36098802 PMCID: PMC9469829 DOI: 10.1007/s00705-022-05575-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 06/04/2022] [Indexed: 12/14/2022]
Abstract
Hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Hepatitis E is an enterically transmitted zoonotic disease that causes large waterborne epidemic outbreaks in developing countries and has become an increasing public-health concern in industrialized countries. In this setting, the infection is usually acute and self-limiting in immunocompetent individuals, although chronic cases in immunocompromised patients have been reported, frequently associated with several extrahepatic manifestations. Moreover, extrahepatic manifestations have also been reported in immunocompetent individuals with acute HEV infection. HEV belongs to the alphavirus-like supergroup III of single-stranded positive-sense RNA viruses, and its genome contains three partially overlapping open reading frames (ORFs). ORF1 encodes a nonstructural protein with eight domains, most of which have not been extensively characterized: methyltransferase, Y domain, papain-like cysteine protease, hypervariable region, proline-rich region, X domain, Hel domain, and RNA-dependent RNA polymerase. ORF2 and ORF3 encode the capsid protein and a multifunctional protein believed to be involved in virion release, respectively. The novel ORF4 is only expressed in HEV genotype 1 under endoplasmic reticulum stress conditions, and its exact function has not yet been elucidated. Despite important advances in recent years, the biological and molecular processes underlying HEV replication remain poorly understood, primarily due to a lack of detailed information about the functions of the viral proteins and the mechanisms involved in host-pathogen interactions. This review summarizes the current knowledge concerning HEV proteins and their biological properties, providing updated detailed data describing their function and focusing in detail on their structural characteristics. Furthermore, we review some unclear aspects of the four proteins encoded by the ORFs, highlighting the current key information gaps and discussing potential novel experimental strategies for shedding light on those issues.
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Affiliation(s)
- Florencia Cancela
- grid.11630.350000000121657640Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Ofelia Noceti
- grid.414402.70000 0004 0469 0889Programa Nacional de Trasplante Hepático y Unidad Docente Asistencial Centro Nacional de Tratamiento Hepatobiliopancreatico. Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - Juan Arbiza
- grid.11630.350000000121657640Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Santiago Mirazo
- grid.11630.350000000121657640Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay ,grid.11630.350000000121657640Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay ,Av. Alfredo Navarro 3051, PC 11600 Montevideo, Uruguay
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31
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Tsakiri M, Naziris N, Demetzos C. Innovative vaccine platforms against infectious diseases: Under the scope of the COVID-19 pandemic. Int J Pharm 2021; 610:121212. [PMID: 34687816 PMCID: PMC8527590 DOI: 10.1016/j.ijpharm.2021.121212] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/06/2021] [Accepted: 10/15/2021] [Indexed: 12/30/2022]
Abstract
While classic vaccines have proved greatly efficacious in eliminating serious infectious diseases, innovative vaccine platforms open a new pathway to overcome dangerous pandemics via the development of safe and effective formulations. Such platforms play a key role either as antigen delivery systems or as immune-stimulators that induce both innate and adaptive immune responses. Liposomes or lipid nanoparticles, virus-like particles, nanoemulsions, polymeric or inorganic nanoparticles, as well as viral vectors, all belong to the nanoscale and are the main categories of innovative vaccines that are currently on the market or in clinical and preclinical phases. In this paper, we review the above formulations used in vaccinology and we discuss their connection with the development of safe and effective prophylactic vaccines against SARS-CoV-2.
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Affiliation(s)
- Maria Tsakiri
- Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece
| | - Nikolaos Naziris
- Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece
| | - Costas Demetzos
- Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece.
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Shafat Z, Hamza A, Islam A, Al-Dosari MS, Parvez MK, Parveen S. Structural exploration of Y-domain reveals its essentiality in HEV pathogenesis. Protein Expr Purif 2021; 187:105947. [PMID: 34314826 DOI: 10.1016/j.pep.2021.105947] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/08/2021] [Accepted: 07/21/2021] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus (HEV) is a major causative agent of hepatitis E infections across the globe. Although the essentiality of HEV nonstructural polyprotein (pORF1) putative Y-domain (Yd) has been established in viral pathogenesis, its structural-functional role remains elusive. The current research discusses the novel exploration on Yd protein expression, purification, biophysical characterization and structure-based docking analysis. The codon optimized synthetic gene and optimized expression parameters i.e., 5 h induction with 0.25 mM IPTG at 37 °C, resulted in efficient production of Yd protein (~40 kDa) in E. coli BL21(DE3) cells. Majority of the recombinant Yd (rYd) protein expressed as inclusion bodies was solubilized in 0.5% N-lauroylsarcosine and purified using Ni-NTA chromatography. Circular dichroism (CD) and UV visible absorption spectroscopic studies on Yd revealed both secondary and tertiary structure stability in alkaline range (pH 8.0-10.0), suggesting correlation with its physiological activity. Thus, loss in structure at low pH perhaps play crucial role in cytoplasmic-membrane interaction. The biophysical data were in good agreement with insilico structural analyses, which suggested mixed α/β fold, non-random and basic nature of Yd protein. Furthermore, due to Yd protein essentiality in HEV replication and pathogenesis, it was considered as a template for docking and drug-likeness analyses. The 3D modeling of Yd protein and structure-based screening and drug-likeness of inhibitory compounds, including established antiviral drugs led to the identification of top nine promising candidates. Nonetheless, in vitro studies on the predicted interaction of Yd with intracellular-membrane towards establishing replication-complexes as well as validations of the proposed therapeutic agents are warranted.
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Affiliation(s)
- Zoya Shafat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Abu Hamza
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Mohammed S Al-Dosari
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad K Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
| | - Shama Parveen
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
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Glitscher M, Hildt E. Hepatitis E virus egress and beyond - the manifold roles of the viral ORF3 protein. Cell Microbiol 2021; 23:e13379. [PMID: 34272798 DOI: 10.1111/cmi.13379] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/18/2021] [Accepted: 07/06/2021] [Indexed: 11/30/2022]
Abstract
Although the hepatitis E virus represents an uprising threat to the global community by representing the commonest cause of an acute viral hepatitis worldwide, its life cycle is grossly understudied. Albeit HEV is a non-enveloped virus, its progeny is released as quasi-enveloped virions. Thus, the responsible accessory protein pORF3 gained rising attention in the past years. It mediates viral release via the exosomal route by targeting the viral capsid to the endosomal system, more precisely to multivesicular bodies. As this is followed by quasi-envelopment, pORF3 may in terms represent a substitute to a conventional envelope protein. This feature proofs to be rather unique with respect to other enteric viruses, although the protein's role in the viral life cycle seems to reach far beyond simply maintaining release of progeny viruses. How pORF3 affects viral morphogenesis, how it mediates efficient viral release and how it supports viral spread is summarised in this microreview. With this, we aim to shed light on functions of pORF3 to gain further insights in still enigmatic aspects of the HEV life cycle. TAKE AWAYS: HEV is released as exosome via multivesicular bodies Viral pORF3 mediates release via endosomal complexes required for transport pORF3 modulates various cellular processes in infected cells Elucidation of pORF3-related processes imply novel clinical strategies.
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Affiliation(s)
| | - Eberhard Hildt
- Department Virology, Paul-Ehrlich-Institut, Langen, Germany
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Antigenic Characterization of ORF2 and ORF3 Proteins of Hepatitis E Virus (HEV). Viruses 2021; 13:v13071385. [PMID: 34372591 PMCID: PMC8310276 DOI: 10.3390/v13071385] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 11/17/2022] Open
Abstract
To evaluate the antigenic properties of Hepatitis E Virus (HEV) Open Reading Frame 2 and 3 (ORF2 and ORF3) codified proteins, we expressed different portions of ORF2 and the entire ORF3 in E. coli, a truncated ORF2, was also expressed in baculovirus. A panel of 37 monoclonal antibodies (MAbs) was raised against ORF2 (1-660 amino acids) and MAbs were mapped and characterized using the ORF2 expressed portions. Selected HEV positive and negative swine sera were used to evaluate ORF2 and ORF3 antigens' immunogenicity. The MAbs were clustered in six groups identifying six antigenic regions along the ORF2. Only MAbs binding to the sixth ORF2 antigenic region (394-608 aa) were found to compete with HEV positive sera and efficiently catch the recombinant antigen expressed in baculovirus. The ORF2 portion from 394-608 aa demonstrated to include most immunogenic epitopes with 85% of HEV positive swine sera reacting against the region from 461-544 aa. Only 5% of the selected HEV sera reacted against the ORF3 antigen.
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Production of capsid proteins of rat hepatitis E virus in Escherichia coli and characterization of self-assembled virus-like particles. Virus Res 2021; 302:198483. [PMID: 34146611 DOI: 10.1016/j.virusres.2021.198483] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/09/2021] [Accepted: 06/10/2021] [Indexed: 12/19/2022]
Abstract
Rat hepatitis E virus (HEV) has been isolated from wild rats worldwide and the potential of zoonotic transmission has been documented. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles. However, the production of rat HEV ORF2 proteins in E. coli forming virus-like particles (VLPs) has not yet been reported. In this study, nine rat HEV ORF2 proteins of the ratELOMB-131L strain with truncated N- and C-termini (amino acids 339-594, 349-594, 351-594, 354-594, 357-594, 357-599, 357-604, 357-609, and 357-614 of ORF2 protein) were expressed in E. coli and the 357-614 protein self-assembled most efficiently. A bioanalyzer showed that the purified 357-614 protein has a molecular weight of 33.5 kDa and a purity of 93.2%. Electron microscopy revealed that the purified 33.5 kDa protein formed VLPs with a diameter of 21-52 (average 32) nm, and immunoelectron microscopy using an anti-rat HEV ORF2 monoclonal antibody (TA7014) indicated that the observed VLPs were derived from rat HEV ORF2. The VLPs attached to and entered the PLC/PRF/5 cells and blocked the neutralization of rat HEV by TA7014, suggesting that the VLPs possess the antigenic structure of infectious rat HEV particles. In addition, rat HEV VLPs showed high immunogenicity in mice. The present results would be useful for future studies on the development of VLP-based vaccines for HEV prevention in a rat model and for the prevention of rat HEV infection in humans.
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Fagan O, Amstrong P, Merwe KVD, Crosnoi D, Steele C, Sopena-Falco J, Parihar V. Viral hepatitis: A brief introduction, review of management, advances and challenges. World J Meta-Anal 2021; 9:139-151. [DOI: 10.13105/wjma.v9.i2.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/26/2021] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
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Ahmad T, Nasir S, Musa TH, AlRyalat SAS, Khan M, Hui J. Epidemiology, diagnosis, vaccines, and bibliometric analysis of the 100 top-cited studies on Hepatitis E virus. Hum Vaccin Immunother 2021; 17:857-871. [PMID: 32755437 PMCID: PMC7993234 DOI: 10.1080/21645515.2020.1795458] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/27/2020] [Accepted: 07/08/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION In low-income countries, Hepatitis E infection is a common cause of acute hepatitis. So far, only two recombinant vaccines (rHEV and HEV 239) have been developed against Hepatitis E virus (HEV). Of which HEV 239 is licensed in China, but is not yet available in any other country. OBJECTIVE This study aims to discuss epidemiology, diagnosis, available vaccines for HEV, and provides an overview of 100 top-cited studies on HEV. METHODS A bibliometric analysis was conducted on the topic "HEV" through a systematic search of the Web of Science. The keywords used were "Hepatitis E" and retrieved articles were assessed for number of attributes. RESULTS The search returned a total of 3,235 publications, cited 95,858 times with h-index 129. The main finding for the 100 top-cited articles on HEV showed: number of authors ranging from 1 to 23, cited references range from 4 to 304, global citations score per year range from 6.61 to 175, and global citations score range from 148 to 791. Of the 100 top-cited studies, the authors who published most articles are Purcell (n = 18), Meng (n = 17), and Emerson (n = 15). Most The largest share of articles on HEV was contributed by United States of America (n = 49) with 12,795 citations. The National Institute of Allergy andInfectious Diseases was leading institute with greatest number of publications (n = 16), cited 3,950 times. CONCLUSIONS The studies conducted on HEV have increased over time. The information presented would be very useful in decision making for policy makers providing health care, and for academicians in providing a reference point for future research.
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Affiliation(s)
- Tauseef Ahmad
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Saima Nasir
- Allama Iqbal Open University, Islamabad, Islamic Republic of Pakistan
| | - Taha Hussein Musa
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | | | - Muhammad Khan
- Department of Genetics, Centre for Human Genetics, Hazara University, Mansehra, Khyber Pakhtunkhwa, Islamic Republic of Pakistan
| | - Jin Hui
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
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Rani D, Nayak B, Srivastava S. Immunogenicity of gold nanoparticle-based truncated ORF2 vaccine in mice against Hepatitis E virus. 3 Biotech 2021; 11:49. [PMID: 33457173 PMCID: PMC7799426 DOI: 10.1007/s13205-020-02573-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 12/01/2020] [Indexed: 12/17/2022] Open
Abstract
This study presents nanoparticle-based vaccine development for Hepatitis E virus (HEV). Gold nanoparticles (GNP) of average size 12 nm were synthesized by citrate reduction method followed by functionalization with cysteamine hydrochloride for nano-conjugation. Immune response of nano-conjugates of GNP with 26 kDa protein (368-606 amino acids) and 54 kDa protein (112-606 amino acids) were evaluated. In vitro release kinetics of GNP-conjugated 54 kDa (GNP54) and 26 kDa (GNP26) proteins showed slower rate of release of 54 kDa protein as compared to 26 kDa protein. Humoral immune response of mice immunized intramuscularly with GNP54, GNP26 and GNP alone, exhibited HEV-specific IgG titer of 7.9 ± 2.9, 5.686 ± 4.098 and 0.698 ± 0.089, respectively, after 14 days of booster immunization. In addition to this, HEV-specific cell-mediated immune response was demonstrated by splenocyte proliferation assay. Analysis of results using one-way ANOVA, showed statistically significant (p value < 0.05) increase in splenocyte proliferation for GNP54- and GNP26-immunized mice in comparison to GNP alone immunized mice. Stimulation index of HEV ORF2 proteins in GNP54/GNP26-immunized mice were comparable to Concanavalin A-treated positive control. These results indicate GNP-based vaccine as a promising candidate for efficiently mediating both humoral and cell-mediated immune response against HEV.
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Terrault NA, Levy MT, Cheung KW, Jourdain G. Viral hepatitis and pregnancy. Nat Rev Gastroenterol Hepatol 2021; 18:117-130. [PMID: 33046891 DOI: 10.1038/s41575-020-00361-w] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2020] [Indexed: 02/06/2023]
Abstract
The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.
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Affiliation(s)
- Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, USA.
| | - Miriam T Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, University of New South Wales, Sydney, New South Wales, Australia
| | - Ka Wang Cheung
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong
| | - Gonzague Jourdain
- French National Research Institute for Sustainable Development (IRD), Marseille, France.,Chiang Mai University, Chiang Mai, Thailand
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40
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Kirkwood CD, Dobscha KR, Steele AD. Hepatitis E should be a global public health priority: recommendations for improving surveillance and prevention. Expert Rev Vaccines 2021; 19:1129-1140. [PMID: 33441054 DOI: 10.1080/14760584.2020.1874930] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Hepatitis E virus (HEV) is an important cause of enterically transmitted viral hepatitis and a significant contributor to maternal mortality in endemic regions around the world, yet the global response has been limited. HEV is a disease of poverty, and the populations experiencing the greatest burden of HEV-associated illness are not benefitting from existing interventions, including WASH strategies and immunization. AREAS COVERED Though a vaccine exists (HEV 239, Hecolin®, Xiamen Innovax Biotech, China), it is only licensed and available in the private market in China and has yet to be prequalified by the WHO for use in endemic settings and outbreaks. This review of the current state of HEV disease and subsequent recommendations for a coordinated public health response are intended to guide the global health community towards breaking the current 'vicious cycle,' in which a lack of data prevents actions that would improve health outcomes. EXPERT OPINION Vaccine implementation in future outbreaks, targeted studies assessing vaccine effectiveness and immunogenicity in endemic regions and populations, improved understanding of the global burden, and improvements in diagnostic and epidemiologic tools are urgently needed. Strategies for implementing routine vaccination programs, improving water, sanitation, and hygiene in endemic regions.
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Affiliation(s)
- Carl D Kirkwood
- Enteric and Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation , Seattle, WA, USA
| | - Katherine R Dobscha
- Enteric and Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation , Seattle, WA, USA
| | - A Duncan Steele
- Enteric and Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation , Seattle, WA, USA
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Minakshi P, Ghosh M, Kumar R, Brar B, Lambe UP, Banerjee S, Ranjan K, Kumar B, Goel P, Malik YS, Prasad G. An Insight into Nanomedicinal Approaches to Combat Viral Zoonoses. Curr Top Med Chem 2021; 20:915-962. [PMID: 32209041 DOI: 10.2174/1568026620666200325114400] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 12/31/2019] [Accepted: 12/31/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.
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Affiliation(s)
- Prasad Minakshi
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar-125001, Haryana, 125004, India
| | - Mayukh Ghosh
- Department of Veterinary Physiology and Biochemistry, RGSC, Banaras Hindu University, Mirzapur (UP) - 231001, India
| | - Rajesh Kumar
- Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar-125001, Haryana, 125004, India
| | - Basanti Brar
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar-125001, Haryana, 125004, India
| | - Upendra P Lambe
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar-125001, Haryana, 125004, India
| | - Somesh Banerjee
- Department of Veterinary Microbiology, Immunology Section, LUVAS, Hisar-125004, India
| | - Koushlesh Ranjan
- Department of Veterinary Physiology and Biochemistry, Sardar Vallabhbhai Patel University of Agriculture and Technology, Meerut, 250110, India
| | | | - Parveen Goel
- Department of Veterinary Medicine, LLR University of Veterinary and Animal Sciences, Hisar, Haryana, 125004, India
| | - Yashpal S Malik
- Division of Standardisation, Indian Veterinary Research Institute Izatnagar - Bareilly (UP) - 243122, India
| | - Gaya Prasad
- Sardar Vallabhbhai Patel University of Agriculture and Technology, Meerut, UP, 250110, India
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Zahmanova G, Mazalovska M, Takova K, Toneva V, Minkov I, Peyret H, Lomonossoff G. Efficient Production of Chimeric Hepatitis B Virus-Like Particles Bearing an Epitope of Hepatitis E Virus Capsid by Transient Expression in Nicotiana benthamiana. Life (Basel) 2021; 11:life11010064. [PMID: 33477348 PMCID: PMC7830250 DOI: 10.3390/life11010064] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/13/2021] [Accepted: 01/14/2021] [Indexed: 12/12/2022] Open
Abstract
The core antigen of hepatitis B virus (HBcAg) is capable of self-assembly into virus-like particles (VLPs) when expressed in a number of heterologous systems. Such VLPs are potential carriers of foreign antigenic sequences for vaccine design. In this study, we evaluated the production of chimeric HBcAg VLPs presenting a foreign epitope on their surface, the 551–607 amino acids (aa) immunological epitope of the ORF2 capsid protein of hepatitis E virus. A chimeric construct was made by the insertion of 56 aa into the immunodominant loop of the HBcAg. The sequences encoding the chimera were inserted into the pEAQ-HT vector and infiltrated into Nicotiana benthamiana leaves. The plant-expressed chimeric HBcHEV ORF2 551–607 protein was recognized by an anti-HBcAg mAb and anti-HEV IgG positive swine serum. Electron microscopy showed that plant-produced chimeric protein spontaneously assembled into “knobbly” ~34 nm diameter VLPs. This study shows that HBcAg is a promising carrier platform for the neutralizing epitopes of hepatitis E virus (HEV) and the chimeric HBcAg/HEV VLPs could be a candidate for a bivalent vaccine.
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Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria; (M.M.); (K.T.); (V.T.)
- Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria;
- Correspondence: (G.Z.); (G.L.); Tel.: +359-32-261529 (G.Z.); +44-1603-450351 (G.L.)
| | - Milena Mazalovska
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria; (M.M.); (K.T.); (V.T.)
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria; (M.M.); (K.T.); (V.T.)
| | - Valentina Toneva
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria; (M.M.); (K.T.); (V.T.)
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Ivan Minkov
- Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria;
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Hadrien Peyret
- Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney NR4 7UH, UK;
| | - George Lomonossoff
- Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney NR4 7UH, UK;
- Correspondence: (G.Z.); (G.L.); Tel.: +359-32-261529 (G.Z.); +44-1603-450351 (G.L.)
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Xu M, Sun L, Wang Y, Gao S, Yang W, Li M. Different mutations at position 562 of the hepatitis E virus capsid proteins exhibit differential effects on viral neutralizing activity. Exp Ther Med 2020; 21:110. [PMID: 33335573 PMCID: PMC7739852 DOI: 10.3892/etm.2020.9542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 10/16/2020] [Indexed: 11/15/2022] Open
Abstract
The hepatitis E virus (HEV) capsid protein pORF2 comprises three potential N-linked glycosylation sites. One site, N562, is located at the cell attachment and neutralizing antigenic regions. The present study performed detailed analyses of the effects of specific amino acid substitutions at position 562 in the homodimerization, glycosylation, antigenicity, immunogenicity and neutralization activities of HEV pORF2. Recombinant HEV pORF2 glycoprotein E1 (amino acids 439-617) and three mutant variants (N562L, N562C and N562K) were expressed in Pichia pastoris (P. pastoris) and SDS-PAGE, Western blot analysis, tunicamycin assay, double-antibody sandwich ELISA and in vitro PCR-based neutralization assay were performed to characterize the different constructs. All proteins were indicated to be secreted by P. pastoris and formed homodimers. Tunicamycin assay revealed the glycosylated status of the wild-type protein, but the mutants were indicated to be non-glycosylated. All proteins were immunoreactive with a neutralizing monoclonal antibody but were not recognized by the antibody after denaturation into monomers. An in vitro PCR-based neutralization assay using mouse antibodies indicated efficient neutralization against N562L, whereas antibodies against N562C and N562K were revealed to be non-neutralizing. Collectively, the present study indicated that specific amino acid substitutions at position 562 serve crucial roles in the activity of the HEV neutralizing epitope.
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Affiliation(s)
- Mingjie Xu
- Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250013, P.R. China
| | - Lizhi Sun
- Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250013, P.R. China
| | - Yan Wang
- Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250013, P.R. China
| | - Shuchun Gao
- Department of Liver Disease, Jinan Infectious Disease Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.,Department of Digestive Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Weihua Yang
- Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250013, P.R. China
| | - Meng Li
- Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250013, P.R. China
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Ngo DB, Chaibun T, Yin LS, Lertanantawong B, Surareungchai W. Electrochemical DNA detection of hepatitis E virus genotype 3 using PbS quantum dot labelling. Anal Bioanal Chem 2020; 413:1027-1037. [PMID: 33236225 DOI: 10.1007/s00216-020-03061-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 12/30/2022]
Abstract
The aim of this study was to develop a highly specific electrochemical DNA sensor using functionalized lead sulphide (PbS) quantum dots for hepatitis E virus genotype 3 (HEV3) DNA target detection. Functionalized-PbS quantum dots (QDs) were used as an electrochemical label for the detection of HEV3-DNA target by the technique of square wave anodic stripping voltammetry (SWASV). The functionalized-PbS quantum dots were characterized by UV-vis, FTIR, XRD, TEM and zeta potential techniques. As-prepared, functionalized-PbS quantum dots have an average size of 4.15 ± 1.35 nm. The detection platform exhibited LOD and LOQ values of 1.23 fM and 2.11 fM, respectively. HEV3-DNA target spiked serum is also reported.Graphical abstract.
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Affiliation(s)
- Duy Ba Ngo
- School of Bioresources and Technology, King Mongkut's University of Technology Thonburi (KMUTT), Bangkhuntien-Chaitalay Road, Bangkok, 10150, Thailand
| | - Thanyarat Chaibun
- Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Phutthamonthon, Nakhon Pathom, 73170, Thailand
| | - Lee Su Yin
- Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Jalan, Bukit Air Nasi, 08100, Bedong, Kedah, Malaysia
| | - Benchaporn Lertanantawong
- Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Phutthamonthon, Nakhon Pathom, 73170, Thailand.
| | - Werasak Surareungchai
- School of Bioresources and Technology, King Mongkut's University of Technology Thonburi (KMUTT), Bangkhuntien-Chaitalay Road, Bangkok, 10150, Thailand. .,Nanoscience and Nanotechnology Graduate Program, Faculty of Science, King Mongkut's University of Technology Thonburi, Pracha Uthit Rd, Bangkok, 10140, Thailand.
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Wen J, Lu W, Meng J. Establishment of competitive binding assay to detect and differentiate hepatitis E virus infection. Ann Hepatol 2020; 18:590-594. [PMID: 31126881 DOI: 10.1016/j.aohep.2019.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES This study was undertaken to demonstrate a promising approach for detection and differentiation the serum immunoglobulin G (IgG) against hepatitis E virus (anti-HEV IgG) using a competitive binding assay established with known genotype-specific monoclonal antibodies (mAbs) 2B1 and 4C5. MATERIALS AND METHODS The mAb 2B1 derived from genotype 1 hepatitis E virus (HEV) antigen and specifically reacted with genotype 1, 2 antigens; 4C5 induced by genotype 4 HEV antigen was specific to genotypes 3, 4 antigens. The 2B1 and 4C5 were labeled with Horseradish peroxidase (HRP), respectively. Subsequently, the titers of coated antigens and HRP-conjugated mAbs for establishment of competitive binding assay were determined by enzyme linked immunosorbent assay (ELISA). And then, the competitive binding assay was performed to assess the inhibition percentage of mAbs binding to antigens inhibited by different genotypes anti-HEV IgG. RESULTS The results of competitive binding assay revealed that genotype 1 anti-HEV IgG could inhibit the binding of mAb 2B1 to genotype 1 antigen more strongly than that of mAb 4C5 to genotype 4 antigen. Whereas, the genotype 3 or 4 anti-HEV IgG could inhibit the binding of mAb 4C5 to genotype 4 antigen more remarkably than that of mAb 2B1 to genotype 1 antigen. CONCLUSIONS These findings provided us a valuable approach for detection and differentiation the HEV infection derived from genotypes 1, 2 (human) or genotypes 3, 4 (zoonosis).
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Affiliation(s)
- Jiyue Wen
- Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China
| | - Weizhuo Lu
- Department of Medical Branch, Hefei Technology College, Hefei, Anhui, China
| | - Jihong Meng
- Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China.
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Abstract
Viral hepatitis can cause a wide spectrum of clinical presentations from a benign form with minimal or no symptoms to acute liver failure or death. Hepatitis D coinfection and superinfection have distinct clinical courses, with the latter more likely leading to chronic infection. Management of chronic hepatitis D virus is individualized because of the paucity of treatment options and significant side effect profile of currently available treatments. Sporadic cases of hepatitis E caused by contaminated meats are becoming increasingly prevalent in immunocompromised hosts. Human herpesviruses are an important cause of disease also in immunocompromised individuals.
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Progress in the Production of Virus-Like Particles for Vaccination against Hepatitis E Virus. Viruses 2020; 12:v12080826. [PMID: 32751441 PMCID: PMC7472025 DOI: 10.3390/v12080826] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/16/2020] [Accepted: 07/28/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E virus (HEV), a pathogen that causes acute viral hepatitis, is a small icosahedral, quasi-enveloped, positive ssRNA virus. Its genome has three open reading frames (ORFs), with ORF1 and ORF3 encoding for nonstructural and regulatory proteins, respectively, while ORF2 is translated into the structural, capsid protein. ORF2 is most widely used for vaccine development in viral hepatitis. Hepatitis E virus-like particles (VLPs) are potential vaccine candidates against HEV infection. VLPs are composed of capsid subunits mimicking the natural configuration of the native virus but lack the genetic material needed for replication. As a result, VLPs are unable to replicate and cause disease, constituting safe vaccine platforms. Currently, the recombinant VLP-based vaccine Hecolin® against HEV is only licensed in China. Herein, systematic information about the expression of various HEV ORF2 sequences and their ability to form VLPs in different systems is provided.
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Patterson J, Hussey HS, Silal S, Goddard L, Setshedi M, Spearman W, Hussey GD, Kagina BM, Muloiwa R. Systematic review of the global epidemiology of viral-induced acute liver failure. BMJ Open 2020; 10:e037473. [PMID: 32690747 PMCID: PMC7375632 DOI: 10.1136/bmjopen-2020-037473] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES The aetiology and burden of viral-induced acute liver failure remains unclear globally. It is important to understand the epidemiology of viral-induced ALF to plan for clinical case management and case prevention. PARTICIPANTS This systematic review was conducted to synthesize data on the relative contribution of different viruses to the aetiology of viral-induced acute liver failure in an attempt to compile evidence that is currently missing in the field. EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science were searched for relevant literature published from 2009 to 2019. The initial search was run on 9 April 2019 and updated via PubMed on 30 September 2019 with no new eligible studies to include. Twenty-five eligible studies were included in the results of this review. RESULTS This systematic review estimated the burden of acute liver failure after infection with hepatitis B virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, herpes simplex virus/human herpesvirus, cytomegalovirus, Epstein-Barr virus and parvovirus B19. Data were largely missing for acute liver failure after infection with varicella-zostervirus, human parainfluenza viruses, yellow fever virus, coxsackievirus and/or adenovirus. The prevalence of hepatitis A-induced acute liver failur was markedly lower in countries with routine hepatitis A immunisation versus no routine hepatitis A immunisation. Hepatitis E virus was the most common aetiological cause of viral-induced acute liver failure reported in this review. In addition, viral-induced acute liver failure had poor outcomes as indicated by high fatality rates, which appear to increase with poor economic status of the studied countries. CONCLUSIONS Immunisation against hepatitis A and hepatitis B should be prioritised in low-income and middle-income countries to prevent high viral-induced acute liver failure mortality rates, especially in settings where resources for managing acute liver failure are lacking. The expanded use of hepatitis E immunisation should be explored as hepatitis E virus was the most common cause of acute liver failure. REGISTRATION PROSPERO registration number: CRD42017079730.
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Affiliation(s)
- Jenna Patterson
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Hannah Sophia Hussey
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Sheetal Silal
- Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
- Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - Liz Goddard
- Department of Paediatrics, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
| | - Mashiko Setshedi
- Department of Medicine, Division of Gastroenterology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Wendy Spearman
- Department of Medicine, Division of Hepatology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Gregory D Hussey
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Benjamin M Kagina
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
| | - Rudzani Muloiwa
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa
- Department of Pediatrics & Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
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49
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Li K, Dong F, Gao F, Bian L, Sun S, Du R, Hu Y, Mao Q, Zheng H, Wu X, Liang Z. Effect of freezing on recombinant hepatitis E vaccine. Hum Vaccin Immunother 2020; 16:1545-1553. [PMID: 31809644 PMCID: PMC7482780 DOI: 10.1080/21645515.2019.1694327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 11/13/2019] [Indexed: 12/19/2022] Open
Abstract
Studies have revealed that vaccines are more often exposed to sub-zero temperatures during cold chain transportation than what was previously known. Such exposure might be detrimental to the potency of temperature-sensitive vaccines. The aim of this study was to evaluate the impact of exposure to freezing on the physicochemical properties and biological activities of recombinant hepatitis E (rHE) vaccine. Changes in rHE vaccine due to freezing temperatures were analyzed with regard to sedimentation rate, antigenicity, and antibody affinity and potency. The freezing temperature of rHE was measured, then rHE vaccine was exposed to freezing temperatures below -10°C.Significant increase of sedimentation rate was noted, according to shake test and massed precipitates. In addition, the binding affinity of rHE vaccine to six specific monoclonal antibodies was significantly reduced and the in vivo potency for eliciting a protective IgG response was also partially lost, especially for anti-HEV neutralizing antibodies. Altogether, our work indicates that exposure of rHE vaccine to a temperature below -10°C results in the loss of structural integrity and biological potency of rHE vaccine.
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Affiliation(s)
- Kelei Li
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
- Research and Development Center, Minhai Biotechnology Co. Ltd, Beijing, China
| | - Fangyu Dong
- The Second Department of Research, Lanzhou Institute of Biological Products Co. Ltd, Lanzhou, China
| | - Fan Gao
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
| | - Lianlian Bian
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
| | - Shiyang Sun
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
| | - Ruixiao Du
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
| | - Yalin Hu
- Quality Assurance Department, Hualan Biological Engineering Inc, Xinxiang, China
| | - Qunying Mao
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
| | - Haifa Zheng
- Research and Development Center, Minhai Biotechnology Co. Ltd, Beijing, China
| | - Xing Wu
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
| | - Zhenglun Liang
- Division of Hepatitis Virus Vaccines, National Institute for Food and Drug Control, Beijing, China
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50
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Demchuk AM, Patel TR. The biomedical and bioengineering potential of protein nanocompartments. Biotechnol Adv 2020; 41:107547. [PMID: 32294494 DOI: 10.1016/j.biotechadv.2020.107547] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 03/21/2020] [Accepted: 04/03/2020] [Indexed: 12/18/2022]
Abstract
Protein nanocompartments (PNCs) are self-assembling biological nanocages that can be harnessed as platforms for a wide range of nanobiotechnology applications. The most widely studied examples of PNCs include virus-like particles, bacterial microcompartments, encapsulin nanocompartments, enzyme-derived nanocages (such as lumazine synthase and the E2 component of the pyruvate dehydrogenase complex), ferritins and ferritin homologues, small heat shock proteins, and vault ribonucleoproteins. Structural PNC shell proteins are stable, biocompatible, and tolerant of both interior and exterior chemical or genetic functionalization for use as vaccines, therapeutic delivery vehicles, medical imaging aids, bioreactors, biological control agents, emulsion stabilizers, or scaffolds for biomimetic materials synthesis. This review provides an overview of the recent biomedical and bioengineering advances achieved with PNCs with a particular focus on recombinant PNC derivatives.
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Affiliation(s)
- Aubrey M Demchuk
- Department of Neuroscience, University of Lethbridge, 4401 University Drive West, Lethbridge, AB, Canada.
| | - Trushar R Patel
- Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming, School of Medicine, University of Calgary, 2500 University Dr. N.W., Calgary, AB T2N 1N4, Canada; Li Ka Shing Institute of Virology and Discovery Lab, Faculty of Medicine & Dentistry, University of Alberta, 6-010 Katz Center for Health Research, Edmonton, AB T6G 2E1, Canada.
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