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Shen L, Zhang Y, Shi M, Shao L, Feng S, Li W, Fang Z, Yin J, Li T. Performance evaluation of the MAGLUMI Hepatitis B virus surface antigen chemiluminescence immunoassay. J Med Virol 2024; 96:e29817. [PMID: 39034740 DOI: 10.1002/jmv.29817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 07/01/2024] [Accepted: 07/09/2024] [Indexed: 07/23/2024]
Abstract
A highly sensitive and reliable Hepatitis B virus surface antigen (HBsAg) measurement is essential to universal screening, timely diagnosis, and management of Hepatitis B virus (HBV) infection. This study aimed to evaluate the performance of MAGLUMI HBsAg chemiluminescence immunoassay (CLIA). MAGLUMI HBsAg (CLIA) was compared against ARCHITECT HBsAg. 411 HBsAg positive samples, including different stages of infection, genotypes, subtypes, mutants, and 30 seroconversion panels were tested to evaluate diagnostic sensitivity. Diagnostic specificity was evaluated by testing 205 hospitalized samples and 5101 blood donor samples. Precision, limit of blank (LoB), limit of detection (LoD), and linearity were also verified. The diagnostic sensitivity of the MAGLUMI HBsAg (CLIA) was 100% with better seroconversion sensitivity than ARCHITECT HBsAg. The MAGLUMI HBsAg (CLIA) has optimal detection efficacy for HBV subgenotypes samples. The analytical sensitivity is 0.039 IU/mL. The initial diagnostic specificity is 99.63% on blood donors and 96.59% on hospitalized samples. The verification data demonstrated high repeatability, a LoB of 0.02 IU/mL, LoD of 0.05 IU/mL and an excellent linearity of 0.050-250 IU/mL (R2 = 0.9946). The MAGLUMI HBsAg (CLIA) is proved a highly sensitive and reliable assay with optimal subgenotype detection efficacy.
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Affiliation(s)
- Lihong Shen
- Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Yun Zhang
- Research & Development Department, Shenzhen New Industries Biomedical Engineering Co. Ltd., Shenzhen, China
| | - Min Shi
- Research & Development Department, Shenzhen New Industries Biomedical Engineering Co. Ltd., Shenzhen, China
| | - Lijia Shao
- Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Shengchun Feng
- Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Weiting Li
- Research & Development Department, Shenzhen New Industries Biomedical Engineering Co. Ltd., Shenzhen, China
| | - Zhonggang Fang
- Research & Development Department, Shenzhen New Industries Biomedical Engineering Co. Ltd., Shenzhen, China
| | - Jun Yin
- Research & Development Department, Shenzhen New Industries Biomedical Engineering Co. Ltd., Shenzhen, China
| | - Tinghua Li
- Research & Development Department, Shenzhen New Industries Biomedical Engineering Co. Ltd., Shenzhen, China
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Lago BV, Portilho MM, Mello VM, De Sousa PSF, Angelice GP, Marques BCL, da Silva Andrade LT, Marques VA, Lewis-Ximenez LL, Mello FCDA, Villar LM. Genetic variability of hepatitis B virus in acute and in different phases of chronic infection in Brazil. Sci Rep 2024; 14:10742. [PMID: 38730249 PMCID: PMC11087654 DOI: 10.1038/s41598-024-60900-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/29/2024] [Indexed: 05/12/2024] Open
Abstract
The selection pressure imposed by the host immune system impacts on hepatitis B virus (HBV) variability. This study evaluates HBV genetic diversity, nucleos(t)ide analogs resistance and HBsAg escape mutations in HBV patients under distinct selective pressures. One hundred and thirteen individuals in different phases of HBV infection were included: 13 HBeAg-positive chronic infection, 9 HBeAg-positive chronic hepatitis, 47 HBeAg-negative chronic infection (ENI), 29 HBeAg-negative chronic hepatitis (ENH) and 15 acute infected individuals. Samples were PCR amplified, sequenced and genetically analyzed for the overlapping POL/S genes. Most HBV carriers presented genotype A (84/113; 74.3%), subgenotype A1 (67/84; 79.7%), irrespective of group, followed by genotypes D (20/113; 17.7%), F (8/113; 7.1%) and E (1/113; 0.9%). Clinically relevant mutations in polymerase (tL180M/M204V) and in the Major Hydrophilic Region of HBsAg (sY100C, T118A/M, sM133T, sD144A and sG145R) were observed. Our findings, however, indicated that most polymorphic sites were located in the cytosolic loops (CYL1-2) and transmembrane domain 4 (TMD4) of HBsAg. Lower viral loads and higher HBV genetic diversity were observed in ENI and ENH groups (p < 0.001), suggesting that these groups are subjected to a higher selective pressure. Our results provide information on the molecular characteristics of HBV in a diverse clinical setting, and may guide future studies on the balance of HBV quasispecies at different stages of infection.
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Affiliation(s)
- Barbara Vieira Lago
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil.
- Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fiocruz, Rio de Janeiro, Brazil.
| | - Moyra Machado Portilho
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Vinicius Motta Mello
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil.
| | - Paulo Sergio Fonseca De Sousa
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Giovana Paula Angelice
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Bianca Cristina Leires Marques
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Larissa Tropiano da Silva Andrade
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Vanessa Alves Marques
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Lia Laura Lewis-Ximenez
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Francisco Campello do Amaral Mello
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
| | - Livia Melo Villar
- Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fiocruz, Hélio and Peggy Pereira Pavillion, Ground Floor, Office B09, FIOCRUZ Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 210360-040, Brazil
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Li H, Qian F, Zou W, Jin F, Li D, Zhang Y. OUP accepted manuscript. Trans R Soc Trop Med Hyg 2022; 116:874-880. [PMID: 35543271 DOI: 10.1093/trstmh/trac040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 02/17/2022] [Accepted: 04/16/2022] [Indexed: 11/14/2022] Open
Affiliation(s)
- Haiyan Li
- Department of Laboratory Medicine, Huzhou Maternity and Child Health Care Hospital, 2 East Street, Huzhou, Zhejiang Province, China
| | - Fuchu Qian
- Department of Precision Medicine, Affiliated Central Hospital Huzhou University, Huzhou Central Hospital, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
- Huzhou Key Laboratory of Molecular Medicine, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
| | - Weihua Zou
- Department of Laboratory Medicine, Affiliated Central Hospital Huzhou University, Huzhou Central Hospital, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
| | - Fang Jin
- Department of Precision Medicine, Affiliated Central Hospital Huzhou University, Huzhou Central Hospital, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
- Huzhou Key Laboratory of Molecular Medicine, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
| | - Dongli Li
- Department of Precision Medicine, Affiliated Central Hospital Huzhou University, Huzhou Central Hospital, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
- Huzhou Key Laboratory of Molecular Medicine, 1558 Sanhuan North Road, Huzhou, Zhejiang Province, China
| | - Yaqin Zhang
- Department of Laboratory Medicine, Huzhou Maternity and Child Health Care Hospital, 2 East Street, Huzhou, Zhejiang Province, China
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Phylogeographic Genetic Diversity in the White Sucker Hepatitis B Virus across the Great Lakes Region and Alberta, Canada. Viruses 2021; 13:v13020285. [PMID: 33673082 PMCID: PMC7918172 DOI: 10.3390/v13020285] [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: 01/12/2021] [Revised: 02/05/2021] [Accepted: 02/08/2021] [Indexed: 12/11/2022] Open
Abstract
Hepatitis B viruses belong to a family of circular, double-stranded DNA viruses that infect a range of organisms, with host responses that vary from mild infection to chronic infection and cancer. The white sucker hepatitis B virus (WSHBV) was first described in the white sucker (Catostomus commersonii), a freshwater teleost, and belongs to the genus Parahepadnavirus. At present, the host range of WSHBV and its impact on fish health are unknown, and neither genetic diversity nor association with fish health have been studied in any parahepadnavirus. Given the relevance of genomic diversity to disease outcome for the orthohepadnaviruses, we sought to characterize genomic variation in WSHBV and determine how it is structured among watersheds. We identified WSHBV-positive white sucker inhabiting tributaries of Lake Michigan, Lake Superior, Lake Erie (USA), and Lake Athabasca (Canada). Copy number in plasma and in liver tissue was estimated via qPCR. Templates from 27 virus-positive fish were amplified and sequenced using a primer-specific, circular long-range amplification method coupled with amplicon sequencing on the Illumina MiSeq. Phylogenetic analysis of the WSHBV genome identified phylogeographical clustering reminiscent of that observed with human hepatitis B virus genotypes. Notably, most non-synonymous substitutions were found to cluster in the pre-S/spacer overlap region, which is relevant for both viral entry and replication. The observed predominance of p1/s3 mutations in this region is indicative of adaptive change in the polymerase open reading frame (ORF), while, at the same time, the surface ORF is under purifying selection. Although the levels of variation we observed do not meet the criteria used to define sub/genotypes of human and avian hepadnaviruses, we identified geographically associated genome variation in the pre-S and spacer domain sufficient to define five WSHBV haplotypes. This study of WSHBV genetic diversity should facilitate the development of molecular markers for future identification of genotypes and provide evidence in future investigations of possible differential disease outcomes.
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Low immunogenic bio-nanocapsule based on hepatitis B virus escape mutants. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2017; 14:595-600. [PMID: 29175598 DOI: 10.1016/j.nano.2017.11.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/22/2017] [Accepted: 11/15/2017] [Indexed: 12/31/2022]
Abstract
Bio-nanocapsules (BNCs) consisting of hepatitis B virus surface antigen (HBsAg) L proteins and phospholipids are used as efficient non-viral carriers for liver-specific delivery of genes and drugs. Considering the administration to HB vaccinees and HB patients, endogenous anti-HBsAg immunoglobulins (HBIGs) may reduce the delivery efficacy and prevent repetitive administration. Therefore, low immunogenic BNCs were generated by inserting two point mutations in the HBsAg L protein, which were found in HBV escape mutants. Escape mutant-type BNC (emBNC) showed 50% lower HBIG binding capacity than that of parental BNC (wtBNC). It induced HBIG production to a lesser extent than that associated with wtBNC in BALB/c mice. The emBNC could accumulate into human hepatocyte-derived tumor in mice pre-treated with HBIGs. The complex of emBNC and cationic liposomes could deliver plasmid DNA to HepG2 cells efficiently in the presence of HBIGs. Thus, emBNC could evade HBIG-neutralizing antibodies, expanding the clinical utility of BNC-based nanomedicine.
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Golsaz-Shirazi F, Amiri MM, Farid S, Bahadori M, Bohne F, Altstetter S, Wolff L, Kazemi T, Khoshnoodi J, Hojjat-Farsangi M, Chudy M, Jeddi-Tehrani M, Protzer U, Shokri F. Construction of a hepatitis B virus neutralizing chimeric monoclonal antibody recognizing escape mutants of the viral surface antigen (HBsAg). Antiviral Res 2017. [DOI: 10.1016/j.antiviral.2017.06.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Elkady A, Iijima S, Aboulfotuh S, Mostafa Ali E, Sayed D, Abdel-Aziz NM, Ali AM, Murakami S, Isogawa M, Tanaka Y. Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt. World J Hepatol 2017; 9:477-486. [PMID: 28396718 PMCID: PMC5368625 DOI: 10.4254/wjh.v9.i9.477] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 09/19/2016] [Accepted: 12/13/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA.
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Affiliation(s)
- Abeer Elkady
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Sayuki Iijima
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Sahar Aboulfotuh
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Elsayed Mostafa Ali
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Douaa Sayed
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Nashwa M Abdel-Aziz
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Amany M Ali
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Shuko Murakami
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Masanori Isogawa
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
| | - Yasuhito Tanaka
- Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt
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De Paschale M, Manco MT, Belvisi L, Cagnin D, Cerulli T, Paganini A, Arpino O, Cianflone A, Agrappi C, Mirri P, Clerici P. Evaluation of LIAISON® XL system for HBsAg, and anti-HCV and anti-HIV/Ag p24. J Med Virol 2016; 89:489-496. [PMID: 27467710 DOI: 10.1002/jmv.24648] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/18/2016] [Indexed: 12/17/2022]
Abstract
The aim of this study was to compare the data obtained using the new LIAISON® XL chemiluminescence system to search for HBsAg, anti-HCV, and anti-HIV1-2/p24 Ag with those obtained using the VITROS system currently adopted by the Microbiology Unit of the Hospital of Legnano. Routine samples of patients who were referred by practitioners for the determination of HBsAg (1,000 samples) and/or anti-HCV (1,002 samples) and/or anti-HIV1-2 (995 samples) were simultaneously analyzed using both systems. The concordant positive and discordant samples were re-examined for confirmation by means of an HBsAg neutralization assay, anti-HCV immunoblot, or anti-HIV1-2 Western blot; HBV-DNA, or HCV-RNA or HIV-RNA was also sought in the discordant samples. Samples of patients known to be positive were tested (100 HBsAg positive, 100 anti-HCV positive, and 100 HIV 1-2 positive) as well throughout treatment, with viremia levels becoming undetectable after treatment. The HBsAg, anti-HCV, and anti-HIV1-2 concordance between the two systems in routine series was respectively 99.8%, 98.5% and 99.7%, and 100% for all markers in samples known positive. The various molecular biology and confirmatory tests of the discordant samples were all negative (except for one anti-HCV positive sample). Measure of Cohen's kappa coefficient for HBsAg, anti-HCV, and anti-HIV gave K values of respectively 0.992, 0.946, and 0.980. In conclusion, the performance of the LIAISON® XL system in the routine laboratory determination for all three markers was comparable with that of the VITROS system. J. Med. Virol. 89:489-496, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | - Maria Teresa Manco
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Luisa Belvisi
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Debora Cagnin
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Teresa Cerulli
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Alessia Paganini
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Olivia Arpino
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Annalisa Cianflone
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Carlo Agrappi
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Paola Mirri
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
| | - Pierangelo Clerici
- Microbiology Unit, ASST Ovest Milanese, Hospital of Legnano, Milan, Italy
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Souza BFDCD, Drexler JF, Lima RSD, Rosário MDOHVD, Netto EM. Theories about evolutionary origins of human hepatitis B virus in primates and humans. Braz J Infect Dis 2014; 18:535-43. [PMID: 24726560 PMCID: PMC9428206 DOI: 10.1016/j.bjid.2013.12.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/12/2013] [Accepted: 12/13/2013] [Indexed: 12/14/2022] Open
Abstract
Introduction The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. Objective To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. Methods This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. Results The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Conclusion Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.
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Affiliation(s)
| | - Jan Felix Drexler
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
| | | | | | - Eduardo Martins Netto
- Infectious Diseases Research Laboratory, University Hospital Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
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Molina Rueda MJ, Jiménez Romano E, Fernández Sierra MA. [De novo hepatitis B due to vaccine-escape mutants in a liver transplant recipient]. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36:546-7. [PMID: 23731979 DOI: 10.1016/j.gastrohep.2013.03.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 03/05/2013] [Indexed: 11/15/2022]
Affiliation(s)
- Maria José Molina Rueda
- Unidad de Gestión Clínica de Medicina Preventiva, Vigilancia y Promoción de la Salud, Granada, España.
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Shi Y, Wei F, Hu D, Li Q, Smith D, Li N, Chen D. Mutations in the major hydrophilic region (MHR) of hepatitis B virus genotype C in North China. J Med Virol 2013; 84:1901-6. [PMID: 23080494 DOI: 10.1002/jmv.23419] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Hepatitis B virus (HBV) can evolve by mutations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) to permit its escape from neutralization by antibodies such as HBV surface antibody (anti-HBs) and from host immune responses. This study investigated the prevalence and pattern of MHR mutations in North China and the clinical correlations of these mutations. The MHRs of 161 HBsAg-positive patients were amplified using nested PCR, and directly sequenced to identify MHR mutations. It was showed that among the 161 patients infected with HBV genotype C in North China, the overall frequency of MHR mutation was 46.6%. Furthermore, MHR mutations were associated with high white blood cell counts (P = 0.025), high bilirubin levels (P = 0.048), and cirrhosis (P = 0.010). The most frequent mutations in patients with both HBsAg-positive and anti-HBs-positive were located in subregion 1 and 3 of MHR, specifically, residue Q101 (29.9%) and I126 (70.6%), which was different from the mutation pattern found in Western Europe and the United States. Taken together, these data indicated important virological and clinical aspects of HBV evolution in terms of the surface gene of genotype C, which might be important for its response to the currently available HBV vaccine.
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Affiliation(s)
- Ying Shi
- Department of Infectious Diseases, Youan Hospital, Capital University of Medical Sciences, Beijing, China
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Chen SM, Kung CM, Yang WJ, Wang HL. Efficacy of the nationwide hepatitis B infant vaccination program in Taiwan. J Clin Virol 2011; 52:11-6. [PMID: 21767983 DOI: 10.1016/j.jcv.2011.06.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2011] [Revised: 06/20/2011] [Accepted: 06/24/2011] [Indexed: 12/17/2022]
Abstract
BACKGROUND Taiwan launched a nationwide infant vaccination program for hepatitis B (HB) in 1984. OBJECTIVES This study evaluated the seroprevalence of hepatitis B virus (HBV) and the incidence of high alanine aminotransferase (ALT) level among young adults prior to, during, and since the introduction of the nationwide HBV vaccination program. STUDY DESIGN Researchers recruited 101,584 freshmen (male:female=1.114:1; mean age, 18.5±0.5 years) from 21 universities between 1995 and 2009 (birth cohorts 1977-1991) in Taiwan, testing for serum hepatitis B surface antigens (HBsAg), hepatitis e antigens (HBeAg), antibodies against HBsAg (anti-HBs), and liver function tests, including ALT and aspartate aminotransferase (AST). RESULTS The results showed that the prevalence of HBsAg decreased significantly from 14.3% in 1995 to 1.1% in 2009 and the seroprevalence of HBeAg decreased significantly from 5.9% in 1995 to 0.3% in 2009. Seroconversion to anti-HBs maintained a steady rate above 50% between 1995 and 2007, but declined considerably to 36.6% and 36.4% in 2008 and 2009, respectively. Subject with HBeAg seropositivity was in 43.94% of HBV carriers. Double seronegativity for HBsAg and anti-HBs was observed in 2007 (47.8%), 2008 (62.3%), and 2009 (62.5%). High ALT level was observed in 5.74% of the subjects, particular among HBV-carriers (16.5% of HBV carrier vs. 5.0% of non-HBV carrier; ORs, 3.733; 95% CIs, 3.463-4.023, p<0.0001). Subjects with high ALT level were significantly positively associated with HBeAg (10.5% of HBeAg seropositive vs. 1.9% of HBeAg seronegative; ORs, 6.195; 95%CI, 5.629-6.818; p<0.0001). Male subjects were more easily infected by HBV than female subjects were (HBsAg, ORs, 1.355, 95% CI, 1.283-1.431; HBeAg, ORs, 1.324, 95% CI, 1.218-1.439, p<0.0001), and significantly more male subjects had high ALT levels than female subjects did (ORs, 4.087; 95% CI, 3.819-4.375, p<0.0001). CONCLUSIONS The mass vaccination program successfully reduced the HBV carrier rate and prevalence of chronic hepatitis B in Taiwan. However, the low percentage of anti-HBV in 2008 and 2009 remains unresolved.
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Affiliation(s)
- Szu-Ming Chen
- Department of Medical Laboratory Science and Biotechnology, College of Biomedical Science and Technology, Yuanpei University, No. 306, Rd. Yuanpei, Hsinchu (300), Taiwan
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Niu J, He S, Su C, Yuan Q, Chen Q, Chen J, Xia N. Variability of the S gene of hepatitis B virus in southeastern China. Arch Virol 2010; 155:1951-7. [DOI: 10.1007/s00705-010-0786-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2009] [Accepted: 08/23/2010] [Indexed: 12/18/2022]
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Acute hepatitis B virus infection with simultaneous high HBsAg and high anti-HBs signals in a previously HBV vaccinated HIV-1 positive patient. J Clin Virol 2010; 47:293-6. [DOI: 10.1016/j.jcv.2009.12.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Revised: 12/01/2009] [Accepted: 12/07/2009] [Indexed: 02/05/2023]
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Kajiwara E, Tanaka Y, Ohashi T, Uchimura K, Sadoshima S, Kinjo M, Mizokami M. Hepatitis B caused by a hepatitis B surface antigen escape mutant. J Gastroenterol 2008; 43:243-247. [PMID: 18373168 DOI: 10.1007/s00535-007-2150-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2007] [Accepted: 12/13/2007] [Indexed: 02/04/2023]
Abstract
Amino acid substitutions within the S gene involving the major antigenic a determinant of the hepatitis B virus (HBV) surface antigen (HBsAg) have been detected in cases of failure of immunization against the virus. Our report showed development of clinical hepatitis in presence of antibody to HBsAg in a healthy individual. A single amino acid substitution (G145R) within the a determinant of the HBsAg was determined by sequencing of the isolated HBV strain. Lamivudine treatment efficiently cleared the peripheral HBV DNA, HBsAg, and hepatitis B e antigen. In conclusion, the immune escape mutant in the S gene can cause hepatitis despite pre-existing naturally acquired immunity.
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Affiliation(s)
- Eiji Kajiwara
- Department of Gastroenterology, Internal Medicine and Pathology, Nippon Steel Yawata Memorial Hospital, 1-1-1 Harunomachi, Kitakyushu, 805-8508, Japan
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Roohi A, Yazdani Y, Khoshnoodi J, Jazayeri SM, Carman WF, Chamankhah M, Rashedan M, Shokri F. Differential reactivity of mouse monoclonal anti-HBs antibodies with recombinant mutant HBs antigens. World J Gastroenterol 2006; 12:5368-74. [PMID: 16981270 PMCID: PMC4088207 DOI: 10.3748/wjg.v12.i33.5368] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the reactivity of a panel of 8 mouse anti-hepatitis B surface antigen (HBsAg) monoclonal antibodies (mAbs) using a collection of 9 recombinant HBsAg mutants with a variety of amino acid substitutions mostly located within the “a” region.
METHODS: The entire HBs genes previously cloned into a mammalian expression vector were transiently transfected into COS7 cells. Two standard unmutated sequences of the ayw and adw subtypes served as controls. Secreted mutant proteins were collected and measured by three commercial diagnostic immunoassays to assess transfection efficiency. Reactivity of anti-HBs mAbs with mutated HBsAgs was determined by sandwich enzyme-linked immunosorbent assay (ELISA).
RESULTS: Reactivity of anti-HBs mAbs with mutated HBsAgs revealed different patterns. While three mutants reacted strongly with all mAbs, two mutants reacted weakly with only two mAbs and the remaining proteins displayed variable degrees of reactivity towards different mAbs. Accordingly, four groups of mAbs with different but overlapping reactivity patterns could be envisaged. One group consisting of two mAbs (37C5-S7 and 35C6-S11) was found to recognize stable linear epitopes conserved in all mutants. Mutations outside the “a” determinant at positions 120 (P→S), 123(T→N) and 161 (M→T) were found to affect reactivity of these mAbs.
CONCLUSION: Our findings could have important implications for biophysical studies, vaccination strategies and immunotherapy of hepatitis B virus (HBV) mutants.
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Affiliation(s)
- Azam Roohi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, PO Box 6446-14133, Tehran, Iran
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Avellón A, Echevarria JM. Frequency of hepatitis B virus 'a' determinant variants in unselected Spanish chronic carriers. J Med Virol 2006; 78:24-36. [PMID: 16299725 DOI: 10.1002/jmv.20516] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The prevalence in the population of hepatitis B virus (HBV) surface antigen (HBsAg) variants that may impair diagnosis, or allow the virus to escape vaccine-induced immunity or passive immunoglobulin therapy is unknown. A genome fragment encoding HBsAg amino acids 112-212 was amplified and sequenced from the sera of 272 unselected DNA-positive, HBV-chronic carriers from Spain. The genotype and the HBsAg subtype were predicted from the sequences. Analysis of amino-acid positions 112-157 revealed single or multiple substitutions in 39% of the carriers studied. Mutations were not detected for residues 121, 135, 137, 139, 140, 141, 142, 146, 147, 148, 149, 151, 152, 153, 155, 156, and 157. Substitutions reported previously to be in association with failures of diagnostic tests or with vaccine or immunoglobulin therapy escape were found in 12.5%, 6.6%, and 9.2% of carriers, respectively. Met133Thr (2.2%); Gln129His, Met133Ile, Phe/Tyr134Asn (1.8%); Phe/Tyr134Leu, Gly145Ala (1.5%), and Pro120Thr (1.1%) were the most frequent. Other substitutions, including Gly145Arg (0.4%), were found at a frequency of less than 1%. Samples containing HBV mutants were tested with three commercial assays for HBsAg screening. Almost all the mutants reacted to the upper cut-off values of the assays, but six samples with weak reactivity with one or more of the methods were also found. Thus, HBV mutants with a potential impact on clinical and public health issues are moderately frequent among chronic carriers from Spain, although their influence on the performance of diagnostic tests seems to be slight.
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Affiliation(s)
- Ana Avellón
- Hepatitis Laboratory, Diagnostic Microbiology Service, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
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Abstract
Hepatitis B viral mutants can emerge in patients as a result of selection pressure from either immune response or treatment options. Mutations that occur within the immunodominant epitopes of hepatitis B surface antigen (HBsAg) allow mutant virus to propagate in the presence of a neutralizing immune response, while wild-type virus is reduced to undetectable levels. HBsAg mutants present as false-negative results in some immunoassays. An understanding of immunoassay reactivity with HBsAg mutants is key to establishing an appropriate testing algorithm for hepatitis B virus detection programs.
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Affiliation(s)
- Paul F Coleman
- Abbott Laboratories, Abbott Park, Illinois 60064-6015, USA.
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Abstract
Hepatitis B viral mutants can emerge in patients as a result of selection pressure from either immune response or treatment options. Mutations that occur within the immunodominant epitopes of hepatitis B surface antigen (HBsAg) allow mutant virus to propagate in the presence of a neutralizing immune response, while wild-type virus is reduced to undetectable levels. HBsAg mutants present as false-negative results in some immunoassays. An understanding of immunoassay reactivity with HBsAg mutants is key to establishing an appropriate testing algorithm for hepatitis B virus detection programs.
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Affiliation(s)
- Paul F Coleman
- Abbott Laboratories, Abbott Park, Illinois 60064-6015, USA.
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Su HX, Xu DZ, Li D, Zhang JX, Lu J, Choi BCK, Yan YP. Heterogeneity analysis of the hepatitis B virus genome in intrauterine infection. J Med Virol 2005; 77:180-7. [PMID: 16121373 DOI: 10.1002/jmv.20454] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
There are many factors leading to intrauterine infection with hepatitis B virus (HBV). These factors include viral structure, HBV mutations, HBV DNA level, placenta barrier, immune status of the mother, and susceptibility of the fetus. The purpose of this study was to investigate the possible relationship between intrauterine infection with and HBV mutations of the genome of the virus. In this study, HBsAg-positive mothers were divided into two groups: intrauterine infection group and non-infection group according to whether the newborn infants were infected or not. The intrauterine infection group included four pairs of mother and their newborn infants infected in utero, and non-infection group included five HBsAg-positive mothers. HBV sequences from the two groups were analyzed and compared. The predominant strains in the mothers and infants from the intrauterine infection group were not completely consistent. This suggested that both HBV predominant strains and minority strains in the mothers could infect their infants through intrauterine transmission. Some HBV mutations probably related to intrauterine infection were examined and it was found that the frequencies of mutations were low in isolates of the virus of infants from the intrauterine infection group and high in the non-infection group. These results suggest that some strains of HBV from the mother may be transmitted selectively to the fetus in utero because of viral heterogeneity. The strains without screened mutations such as P21L in the pre-S1 region may infect the fetus more readily.
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Affiliation(s)
- Hai-Xia Su
- Department of Epidemiology, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an, China
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Fitzsimons D, François G, Hall A, McMahon B, Meheus A, Zanetti A, Duval B, Jilg W, Böcher WO, Lu SN, Akarca U, Lavanchy D, Goldstein S, Banatvala J, Damme PV. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine 2005; 23:4158-66. [PMID: 15964484 DOI: 10.1016/j.vaccine.2005.03.017] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2005] [Accepted: 03/09/2005] [Indexed: 01/05/2023]
Abstract
The long-term efficacy of hepatitis B vaccine, long-term effectiveness of hepatitis B immunisation programmes, immune memory induced by hepatitis B vaccine, current booster policies, and impact of hepatitis B virus mutants on immunisation programmes were reviewed at the Viral Hepatitis Prevention Board (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal vaccination programmes with data being presented from Italy, Saudi Arabia, Singapore, Spain, Taiwan, Thailand, The Gambia, and USA (Alaska).
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Affiliation(s)
- David Fitzsimons
- World Health Organization, Via Appia 20, CH-1211 Geneva, Switzerland
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Yoshikawa A, Gotanda Y, Itabashi M, Minegishi K, Kanemitsu K, Nishioka K. Hepatitis B NAT virus-positive blood donors in the early and late stages of HBV infection: analyses of the window period and kinetics of HBV DNA. Vox Sang 2005; 88:77-86. [PMID: 15720604 DOI: 10.1111/j.1423-0410.2005.00602.x] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES The Japanese Red Cross (JRC) carries out nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1) by using a multiplex (MPX) reagent. Screening is undertaken on serologically negative units. In this study we characterized HBV NAT-positive donations individually and analysed the window period and kinetics of HBV DNA, during acute infection, in follow-up studies. MATERIALS AND METHODS Two hundred and seventy-seven HBV DNA-positive donations have been identified in Japan since the introduction of NAT screening of 50-donation minipools. The viral loads and genotypes of these HBV DNA-positive donations were characterized. The doubling time and half-life of HBV was estimated from the data of 123 follow-up donors. The sensitivity of the NAT system (based on 50-donation minipools) was compared with the sensitivities of the enzyme immunoassay (EIA) and the chemiluminescence immunoassay (CLIA). Samples that were CLIA negative, but with > 10(4) copies/ml of HBV DNA, were analysed by sequencing the hepatitis B surface antigen (HBsAg) region. RESULTS Out of 277 HBV NAT-positive samples, 125 (45%) were found to have an increasing viral load and 45 (16%) a decreasing viral load. Forty per cent of HBV NAT-positive samples with an increasing viral load, and 33% of those with a decreasing viral load, were negative when tested by using the CLIA. No mutations related to escape mutants were found in the samples that were CLIA negative but with HBV DNA loads of > 10(4) copies/ml. The median HBV doubling time was 2.6 days (n = 93, 1.3-15.2 days) and the half-life was 1.6 days (n = 55, 0.9-6.3 days). Some kinetic difference was observed between genotypes A and B. CONCLUSIONS HBV NAT screening detected HBV DNA in both early (the so-called serological window period) and late stages of acute HBV infection.
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Affiliation(s)
- Akira Yoshikawa
- Japanese Red Cross Saitama Blood Center, Hidaka, Saitama, Japan.
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Hu H, Peng XM, Huang YS, Gu L, Xie QF, Gao ZL. Yeast expression and DNA immunization of hepatitis B virus S gene with second-loop deletion of α determinant region. World J Gastroenterol 2004; 10:2989-93. [PMID: 15378779 PMCID: PMC4576258 DOI: 10.3748/wjg.v10.i20.2989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: Immune escape mutations of HBV often occur in the dominant epitope, the second-loop of the a determinant of hepatitis B surface antigen (HBsAg). To let the hosts respond to the subdominant epitopes in HBsAg may be an effective way to decrease the prevalence of immune escape mutants. For this reason, a man-made clone of HBV S gene with the second-loop deletion was constructed. Its antigenicity was evaluated by yeast expression analysis and DNA immunization in mice.
METHODS: HBV S gene with deleted second-loop, amino acids from 139 to 145, was generated using splicing by overlap extension. HBV deleted S gene was then cloned into the yeast expression vector pPIC9 and the mammalian expression vector pcDNA3 to generate pHB-SDY and pHB-SD, respectively. The complete S gene was cloned into the same vectors as controls. The deleted recombinant HBsAg expressed in yeasts was detected using Abbott IMx HBsAg test kits, enzyme-linked immunoadsorbent assay (ELISA) and immune dot blotting to evaluate its antigenicity in vitro. The anti-HBs responses to DNA immunization in BALB/c mice were detected using Abbott IMx AUSAB test kits to evaluate the antigenicity of that recombinant protein in vivo.
RESULTS: Both deleted and complete HBsAg were successfully expressed in yeasts. They were intracellular expressions. The deleted HBsAg could not be detected by ELISA, in which the monoclonal anti-HBs against the α determinant was used, but could be detected by Abbott IMx and immune dot blotting, in which multiple monoclonal anti-HBs and polyclonal anti-HBs were used, respectively. The activity of the deleted HBsAg detected by Abbott IMx was much lower than that of complete HBsAg (the ratio of sample value/cut off value, 106 ± 26.7 vs 1814.4 ± 776.3, P < 0.01, t = 5.02). The anti-HBs response of pHB-SD to DNA immunization was lower than that of complete HBV S gene vector pHB (the positive rate 2/10 vs 6/10, 4.56 ± 3.52 mIU/mL vs 27.60 ± 17.3 mIU/mL, P = 0.02, t = 2.7).
CONCLUSIONS: HBsAg with deleted second-loop of the α determinant still has antigenicity, and can also raise weak anti-HBs response in mice to DNA immunization, suggesting that it is possible to develop a subdominant vaccine for preventing infections of immune escape mutants of HBV.
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Affiliation(s)
- Hui Hu
- Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
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