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Bello N, Hudu SA, Alshrari AS, Imam MU, Jimoh AO. Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review. Pathogens 2024; 13:554. [PMID: 39057781 PMCID: PMC11279426 DOI: 10.3390/pathogens13070554] [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: 05/24/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.
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Affiliation(s)
- Nura Bello
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
- Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria 810107, Nigeria
| | - Shuaibu A. Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Ahmed S. Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Mustapha U. Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
| | - Abdulgafar O. Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
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Rahman T, Das A, Abir MH, Nafiz IH, Mahmud AR, Sarker MR, Emran TB, Hassan MM. Cytokines and their role as immunotherapeutics and vaccine Adjuvants: The emerging concepts. Cytokine 2023; 169:156268. [PMID: 37320965 DOI: 10.1016/j.cyto.2023.156268] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 06/17/2023]
Abstract
Cytokines are a protein family comprising interleukins, lymphokines, chemokines, monokines and interferons. They are significant constituents of the immune system, and they act in accordance with specific cytokine inhibiting compounds and receptors for the regulation of immune responses. Cytokine studies have resulted in the establishment of newer therapies which are being utilized for the treatment of several malignant diseases. The advancement of these therapies has occurred from two distinct strategies. The first strategy involves administrating the recombinant and purified cytokines, and the second strategy involves administrating the therapeutics which inhibits harmful effects of endogenous and overexpressed cytokines. Colony stimulating factors and interferons are two exemplary therapeutics of cytokines. An important effect of cytokine receptor antagonist is that they can serve as anti-inflammatory agents by altering the treatments of inflammation disorder, therefore inhibiting the effects of tumour necrosis factor. In this article, we have highlighted the research behind the establishment of cytokines as therapeutics and vaccine adjuvants, their role of immunotolerance, and their limitations.
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Affiliation(s)
- Tanjilur Rahman
- Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Ayan Das
- Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Mehedy Hasan Abir
- Faculty of Food Science and Technology, Chattogram Veterinary and Animal Sciences University, Chattogram 4225, Bangladesh
| | - Iqbal Hossain Nafiz
- Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Chittagong, Chattogram 4331, Bangladesh
| | - Aar Rafi Mahmud
- Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh
| | - Md Rifat Sarker
- Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chattogram 4381, Bangladesh; Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Mohammad Mahmudul Hassan
- Department of Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Chattogram 4225, Bangladesh; Queensland Alliance for One Health Sciences, School of Veterinary Science, The University of Queensland, Queensland 4343, Australia.
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Fan J, Jin S, Gilmartin L, Toth I, Hussein WM, Stephenson RJ. Advances in Infectious Disease Vaccine Adjuvants. Vaccines (Basel) 2022; 10:1120. [PMID: 35891284 PMCID: PMC9316175 DOI: 10.3390/vaccines10071120] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/01/2022] [Accepted: 07/04/2022] [Indexed: 02/01/2023] Open
Abstract
Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases. Immune stimulants (or adjuvants) are an indispensable factor in vaccine development, especially for inactivated and subunit-based vaccines due to their decreased immunogenicity compared to whole pathogen vaccines. Adjuvants are widely diverse in structure; however, their overall function in vaccine constructs is the same: to enhance and/or prolong an immunological response. The potential for adverse effects as a result of adjuvant use, though, must be acknowledged and carefully managed. Understanding the specific mechanisms of adjuvant efficacy and safety is a key prerequisite for adjuvant use in vaccination. Therefore, rigorous pre-clinical and clinical research into adjuvant development is essential. Overall, the incorporation of adjuvants allows for greater opportunities in advancing vaccine development and the importance of immune stimulants drives the emergence of novel and more effective adjuvants. This article highlights recent advances in vaccine adjuvant development and provides detailed data from pre-clinical and clinical studies specific to infectious diseases. Future perspectives into vaccine adjuvant development are also highlighted.
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Affiliation(s)
- Jingyi Fan
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; (J.F.); (S.J.); (L.G.); (I.T.); (W.M.H.)
| | - Shengbin Jin
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; (J.F.); (S.J.); (L.G.); (I.T.); (W.M.H.)
| | - Lachlan Gilmartin
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; (J.F.); (S.J.); (L.G.); (I.T.); (W.M.H.)
| | - Istvan Toth
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; (J.F.); (S.J.); (L.G.); (I.T.); (W.M.H.)
- Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
- School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia
| | - Waleed M. Hussein
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; (J.F.); (S.J.); (L.G.); (I.T.); (W.M.H.)
| | - Rachel J. Stephenson
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; (J.F.); (S.J.); (L.G.); (I.T.); (W.M.H.)
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Feng Y, Wang J, Shao Z, Chen Z, Yao T, Dong S, Wu Y, Shi X, Shi J, Liu G, Bai J, Guo H, Liu H, Wu X, Liu L, Song X, Zhu J, Wang S, Liang X. Predicting related factors of immunological response to hepatitis B vaccine in hemodialysis patients based on integration of decision tree classification and logistic regression. Hum Vaccin Immunother 2021; 17:3214-3220. [PMID: 33989106 DOI: 10.1080/21645515.2021.1895603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
The non/hypo-response rate of the hepatitis B vaccine among hemodialysis (HD) patients is still high, it is of great significance to explore the influencing factors and their relationships. To study the related factors and their relationships using logistic regression model and Chi-squared Automatic Interaction Detection (CHAID) decision tree model. A randomized controlled trial was conducted between February 2014 and May 2015 in China. HD patients being serologically negative for HBsAg and anti-HBs were randomly assigned to receive three intramuscular injections of the standard dose (20 µg) or high dose (60 µg) of recombinant hepatitis B vaccine at months 0, 1, and 6. Those with anti-HBs concentrations <100 mIU/mL, and ≥100 mIU/mL at month 7 were considered as non/hypo-response and high-level response, respectively. The non/hypo-response was 31.34% (89/284). After adjustment for confounders, logistic analysis showed that males (OR = 2.203, 95%CI: 1.109-4.367) and those with higher dialysis frequency (>4 times per 2 weeks) (OR = 1.918, 95%CI: 1.015-3.626) had a significant risk of non/hypo-response. While the CHAID analysis showed that gender, dose, and dialysis frequency were influencing factors of non/hypo-response, and gender is most important. The interaction between gender and dialysis frequency had the greatest effect on immunization, and followed by the interaction between dialysis frequency and vaccine dose. Taken together, gender, dose and dialysis frequency were influencing factors of hepatitis B vaccine in HD patients.
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Affiliation(s)
- Yongliang Feng
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jianmin Wang
- Department of Nephrology, Linfen Central Hospital, Shanxi, China
| | - Zhihong Shao
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhuanzhuan Chen
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Tian Yao
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Shuang Dong
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yuanting Wu
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaohong Shi
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jing Shi
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Guangming Liu
- Clinical Laboratory, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, China
| | - Jingen Bai
- Department of Nephrology, Lvliang People's Hospital, Lvliang, Shanxi, China
| | - Hongping Guo
- Department of Nephrology, Linfen People's Hospital, Linfen, Shanxi, China
| | - Hongting Liu
- Department of Nephrology, Yuncheng Central Hospital, Yuncheng, Shanxi, China
| | - Xiaofeng Wu
- Department of Nephrology, The Second People's Hospital of Jinzhong, Jinzhong, Shanxi, China
| | - Liming Liu
- Department of Nephrology, Linfen Central Hospital, Shanxi, China
| | - Xiaohui Song
- Department of Nephrology, Fenyang Hospital of Shanxi Province, Fenyang, Shanxi, China
| | - Jiangtao Zhu
- Department of Nephrology, Changzhi Hospital of Traditional Chinese Medicine, Changzhi, Shanxi, China
| | - Suping Wang
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.,Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
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Fabrizi F, Cerutti R, Dixit V, Ridruejo E. Hepatitis B virus vaccine and chronic kidney disease. The advances. Nefrologia 2021; 41:115-122. [PMID: 36165374 DOI: 10.1016/j.nefroe.2020.08.005] [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: 03/14/2020] [Accepted: 08/14/2020] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Hepatitis B is an important agent of liver disease in patients with chronic kidney disease and chronic HBV infection promotes the development of CKD in the adult general population. Patients with CKD have a suboptimal response to various vaccines, and it remains unclear how we boost the immune response of CKD patients to HB vaccine. STUDY AIMS AND DESIGN We performed a narrative review to assess the mechanisms of lower immunogenicity of HBV vaccine in CKD population; multiple approaches to improve the response rate of CKD patients to HBV vaccine have been reported. This is a very important topic for nephrologists who often serve as primary case providers for patients with CKD. RESULTS The recommended vaccine schedule for CKD patients including those on maintenance dialysis is based on recombinant vaccine, four doses (month 0,1,2, and 6; 40mcg each) by intramuscular route (deltoid muscle). According to RCTs or observational studies, some recombinant vaccines with adjuvants (i.e., HBV-AS02 and HBV-AS04) look promising. HBV-AS04 showed to give better seroprotection rates and durable immune response over extended follow-ups compared with licensed HBV vaccine in CKD patients. The seroprotection rate was 95% (97/102) and 82% (202/248) in pre-dialysis and dialysis patients, respectively, one month after completing vaccine schedule with HBV-AS04. HBV-AS02 was superior to licensed vaccine in terms of seroprotection rate, 76.9% vs. 37.6%. CONCLUSIONS We suggest adjuvanted recombinant (HBV-AS04) vaccine (0,1,2 and 3 months; 20 mcg each dose) and post vaccination testing of anti-HBs antibody after vaccination. Booster doses to patients whose anti-HBs titers fall below the seroprotection level (<10IU/mL) during the follow-up are appropriate. The patho-physiologic mechanisms responsible for the poor immunogenicity of HBV vaccine in CKD patients are under active investigation.
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Affiliation(s)
- Fabrizio Fabrizi
- IRCCS Ca' Granda Foundation and Maggiore Polyclinic Hospital, Milano, Italy.
| | - Roberta Cerutti
- IRCCS Ca' Granda Foundation and Maggiore Polyclinic Hospital, Milano, Italy
| | - Vivek Dixit
- Division of Digestive Diseases, UCLA School of Medicine, CA, USA
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC", Ciudad de Buenos Aires, Argentina; Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina; Latin American Liver Research, Educational and Awareness Network (LALREAN), Pilar, Provincia de Buenos Aires, Argentina
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Fabrizi F, Cerutti R, Garcia-Agudo R, Bellincioni C, Porata G, Frontini G, Aoufi-Rabih S, Messa P. Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial. Clin Res Hepatol Gastroenterol 2020; 44:905-912. [PMID: 32144074 DOI: 10.1016/j.clinre.2020.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients on regular dialysis show a poor response to hepatitis B vaccine due to uremia. A recombinant HB vaccine (containing an improved adjuvant system AS04, HBV-AS04) has been licensed but the evidence on its efficacy and safety in dialysis population over the long term is extremely limited. AIM We have measured antibody (anti-HBs) persistence for up to 72 months in a large cohort of patients on long-term dialysis (with susceptibility to HBV infection) who underwent vaccination with HBV-AS04 vaccine. METHODS Patients were prospectively recruited to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle). Two vaccine schedules were adopted: 0,1,2, and 3 month (n=217 patients) and 0,1,2, and 6 month (n=31 patients). Anti-HBs antibody concentrations were tested at 1,2,3, 4, 7 and 12 months and then every year up to 72 months. Multivariate analysis was made to find the baseline parameters that were associated with the immune response to HBV-AS04 vaccine. RESULTS Two hundred and seventy-two patients were included and 248 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 81.5% (202/248) (mean anti-HBs antibody titers, 384.9±391.9mIU/mL), according to per-protocol analysis. On the grounds of univariate analysis, age was lower in responder than non- responder patients to HBV AS04 even if no statistical significance was achieved (P=0.09). The sero-protection rate at month 72 was 77% (7/9) (anti-HBs antibody titers, 184.9±360.1mIU/mL, P=0.001). Multivariate analysis found a relationship between sero-response rate and age (P=0.04). No major side effects and no de novo HBV episodes were observed. CONCLUSIONS Our open-label nonrandomized trial performed in a 'real-world' practice showed the persistence of anti-HBs antibody among responder patients over a very long follow-up. Studies with longer observation periods are under way.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy.
| | - Roberta Cerutti
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | | | - Cecilia Bellincioni
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | - Giulia Porata
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | - Giulia Frontini
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | | | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy; University School of Medicine, Milan, Italy
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ZHANG LINL, GUO JING, DUAN KAI. Comparative analysis of the safety and efficacy of HBsAg-1018 versus HBsAg-Eng: a meta-analysis. Cent Eur J Immunol 2020; 44:455-462. [PMID: 32140059 PMCID: PMC7050062 DOI: 10.5114/ceji.2019.92808] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 04/08/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION In addition to alum adjuvant, a wide diversity of adjuvants have been developed to enhance immune response of hepatitis B virus (HBV) vaccine in varying subjects, either in healthy vaccinators or subjects with hypo-immunity. In this context, a novel HBV vaccine HBsAg-1018, formulated with a toll-like receptor 9 agonist, was developed, and is currently in the phase of clinical trials. So, the first meta-analysis was performed to examine the safety and immune response of HBsAg-1018 among varying subjects. MATERIAL AND METHODS On the basis of inclusion criterion, eligible studies that reported safety and immunogenicity induced by HBsAg-1018 vaccination in randomised, controlled trials (RCTs) were involved from three databases: PubMed, EMBASE, and the Cochrane Library, and further confirmed by two reviewers. Meta-analysis was conducted using RevMan 5.3. The pooled relative risk (RR) for safety and immunogenicity was calculated using random-effects or fixed-effects models according to the heterogeneity of included studies. The methodology quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. RESULTS In total 5073 subjects administrated with HBV vaccine from four eligible publications were included in this meta-analysis. The data related to immunogenicity and safety post vaccination were pooled for meta-analysis. For safety, the combined RRs for adverse reactions were 0.98 (95% CI: 0.89-1.08), 1.02 (95% CI: 0.94-1.10) for AE, 0.88 (95% CI: 0.70-1.10) for SAE, and 1.07 (0.12-9.17) for death. No statistical heterogeneity among RCTs was found (p > 0.05). For immunogenicity, at four weeks post vaccination, seroprotection rates (SPRs) in HBsAg-1018 were significantly superior to the conventional HBV vaccine containing alum adjuvant, HBsAg-Eng (Engerix-B®, GlaxoSmithKline, Rixensart, Belgium) (RR: 4.35; 95% CI: 3.35-5.65). Furthermore, superior immunogenicity of HBsAg-1018 was maintained with RRs up to 1.23 and 95% CI: 1.20-1.27 through 28 weeks post vaccination. However, there was considerable heterogeneity with > 80% I2 value (p < 0.05). CONCLUSIONS In comparison with HBsAg-Eng, HBsAg-1018 exhibited superior immune response and comparable safety profile with HBsAg-Eng in varying subjects. HBsAg-1018 is an effective and safe prophylactic measure to prevent HBV infection.
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Affiliation(s)
- LIN L. ZHANG
- Wuhan Institute of Biological Products Co. Ltd., China
| | - JING GUO
- Wuhan Institute of Biological Products Co. Ltd., China
| | - KAI DUAN
- Wuhan Institute of Biological Products Co. Ltd., China
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Saco TV, Strauss AT, Ledford DK. Hepatitis B vaccine nonresponders: Possible mechanisms and solutions. Ann Allergy Asthma Immunol 2018; 121:320-327. [PMID: 29567355 DOI: 10.1016/j.anai.2018.03.017] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 03/12/2018] [Accepted: 03/13/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Hepatitis B (HBV) is a viral illness that chronically infects 240 million people worldwide, leads to liver disease, and increases risk of hepatocellular carcinoma. The HBV vaccine has decreased HBV infection, and it and the human papilloma virus vaccine are the only vaccines that prevent cancer. Despite the effectiveness of the HBV vaccine, some populations do not develop protective responses. The risk groups for poor response include those with immunosuppression or dialysis-dependent, end-stage renal disease. Five percent of normal people do not have a response. These subjects are deemed HBV "nonresponders." Multiple strategies to improve the immunogenicity of the HBV vaccine are currently being pursued, including vaccine adjuvants, recombinant vaccines, and immune enhancement via up-regulation of dendritic cells. DATA SOURCES PubMed was searched for peer-reviewed publications published from January 1980 to September 2017. STUDY SELECTIONS Studies retrieved for inclusion summarized potential mechanisms behind HBV vaccine nonresponsiveness and potential solutions. RESULTS The mechanisms behind HBV vaccine nonresponsiveness vary between each subject population. Many current and future strategies may provide protective immunity against HBV in each of these populations. CONCLUSION This review provides a background on the immunology of HBV infection, the possible immunologic mechanisms to explain HBV vaccine nonresponsiveness, current research aimed at improving vaccine effectiveness, and possible future approaches for providing nonresponders protection from HBV.
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Affiliation(s)
- Tara Vinyette Saco
- University of South Florida Morsani College of Medicine, and James A. Haley Veterans Hospital, Department of Internal Medicine and Division of Allergy and Immunology, Tampa, Florida.
| | - Alexandra T Strauss
- University of South Florida Morsani College of Medicine, and James A. Haley Veterans Hospital, Department of Internal Medicine and Division of Allergy and Immunology, Tampa, Florida
| | - Dennis K Ledford
- University of South Florida Morsani College of Medicine, and James A. Haley Veterans Hospital, Department of Internal Medicine and Division of Allergy and Immunology, Tampa, Florida
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Kim JU, Kim M, Kim S, Nguyen TT, Kim E, Lee S, Kim S, Kim H. Dendritic Cell Dysfunction in Patients with End-stage Renal Disease. Immune Netw 2017; 17:152-162. [PMID: 28680376 PMCID: PMC5484645 DOI: 10.4110/in.2017.17.3.152] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 04/06/2017] [Accepted: 04/10/2017] [Indexed: 02/07/2023] Open
Abstract
End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients' propensity for infections and malignancies as well as causing a diminished response to vaccination. Several factors influence the immunodeficiency in patients with ESRD, including uremic toxins, malnutrition, chronic inflammation, and the therapeutic dialysis modality. The alteration of T-cell function in ESRD has been considered to be a major factor underlying the impaired adaptive cellular immunity in these patients. However, cumulative evidence has suggested that the immune defect in ESRD can be caused by an Ag-presenting dendritic cell (DC) dysfunction in addition to a T-cell defect. It has been reported that ESRD has a deleterious effect on DCs both in terms of their number and function, although the precise mechanism by which DC function becomes altered in these patients is unclear. In this review, we discuss the effects of ESRD on the number and function of DCs and propose a possible molecular mechanism for DC dysfunction. We also address therapeutic approaches to improve immune function by optimally activating DCs in patients with ESRD.
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Affiliation(s)
- Ji Ung Kim
- Division of Nephrology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju 63241, Korea
| | - Miyeon Kim
- Division of Nephrology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju 63241, Korea
| | - Sinae Kim
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Tam Thanh Nguyen
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Eunhye Kim
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Siyoung Lee
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,YbdYbiotech research center, Seoul 08589, Korea
| | - Soohyun Kim
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Veterinary Science Research Institute, Konkuk University, Seoul 05029, Korea
| | - Hyunwoo Kim
- Division of Nephrology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju 63241, Korea
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Khedmat H, Aghaei A, Ghamar-Chehreh ME, Agah S. Sex bias in response to hepatitis B vaccination in end-stage renal disease patients: Meta-analysis. World J Nephrol 2016; 5:115-124. [PMID: 26788471 PMCID: PMC4707164 DOI: 10.5527/wjn.v5.i1.115] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 06/22/2015] [Accepted: 12/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To systematically review the literature for studies investigating the potential effect of gender of dialysis patients on the immunogenicity of hepatitis B virus vaccines.
METHODS: Literature searches were conducted by the MEDLINE and Google Scholar. The key words used included “hepatitis B (HB)”, “vaccine”, “dialysis”, “hemodialysis”, “sex”, “male” and “female”. Data of seroresponse to HB vaccine in clinical trials regarding sex of the recipients have been achieved and analyzed. Finally data from 19 clinical trials have been pooled and analyzed.
RESULTS: Analysis of response to HB vaccination in our dialysis population showed males significantly respond less to hepatitis B vaccination (P = 0.002, Z = 3.08) with no significant heterogeneity detected [P = 0.766; heterogeneity χ2 = 14.30 (df = 19); I2 = 0%]. A reanalysis of the pooled data was conducted regarding the dialysis mode to evaluate potential differential impact of sex on HB vaccine response. Hemodialysis was the only subgroup that showed a significant difference regarding dialysis mode in response to HB vaccination regarding sex (P = 0.042, Z = 2.03).
CONCLUSION: This Meta-analysis showed significant effect for the sex of chronic kidney disease and dialysis patients on the immunogenicity of HB vaccine. This sex discrimination was most prominent among hemodialysis patients.
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12
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Loustaud-Ratti V, Jacques J, Debette-Gratien M, Carrier P. Hepatitis B and elders: An underestimated issue. Hepatol Res 2016; 46:22-8. [PMID: 25651806 DOI: 10.1111/hepr.12499] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 01/17/2015] [Accepted: 02/02/2015] [Indexed: 12/16/2022]
Abstract
As the world's population becomes older, the burden of hepatitis B virus in elderly has to be considered. The liver changes with aging and its function is eventually altered. The prevalence of hepatitis B virus is paradoxically more important in elderly in areas having vaccination programs, because of a loosening of the prevention in older patients. Some differences in hepatitis B presentation must be enhanced in elderly: lower spontaneous hepatitis B surface antigen clearance after a recent contamination, major risk of cirrhosis and hepatocarcinoma. Acute hepatitis B seems to be more often symptomatic, with a great risk of chronicity. Hepatocarcinoma linked to hepatitis B virus has a higher prevalence and a different presentation in elderly. Its treatment is the same as in younger people but is less often possible. Liver transplantation is contraindicated after 70 years old. Hepatitis B treatment panel is the same as in younger people (pegylated interferon, nucleoside or nucleotide agents). It gives identical results with no particular adverse events if the precautions for use are followed. Vaccination is less efficient, as in immunocompromised patients, and needs specific protocols.
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Affiliation(s)
- Véronique Loustaud-Ratti
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges.,INSERM UMR 850, School of Medicine, Limoges, France
| | - Jérémie Jacques
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges
| | | | - Paul Carrier
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges
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13
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Fabrizi F, Tarantino A, Castelnovo C, Martin P, Messa P. Recombinant Hepatitis B Vaccine Adjuvanted With AS04 in Dialysis Patients: A Prospective Cohort Study. Kidney Blood Press Res 2015; 40:584-92. [PMID: 26566033 DOI: 10.1159/000368534] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2015] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination, including to hepatitis B vaccine. A recombinant HB vaccine containing a new adjuvant system AS04 (HBV-AS04) has been recently developed; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis. All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospectively included. METHODS Patients received four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 0,1,2, and 3. Anti-HB surface antibody concentrations were measured at intervals of 1, 2, 3, 4, and 12 months. Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine. RESULTS 102 patients were enrolled and 91 completed the study. At completion of the vaccination schedule, using per-protocol analysis, 76 of 91 (84%) had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations (GMCs) of 385.25 mIU/mL. The sero-protection rate at month 12 was 84% (48/57) with lower GMCs (62.74 mIU/mL, P<0.0001). Multivariate analysis revealed a detrimental role of age on the immune response to HB-AS04 vaccine (F Ratio, 4.04; P<0.04). Tolerance to HBV-AS04 was good and only minor side-effects were observed. CONCLUSIONS HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present. Prospective studies with HBV-AS04 on larger study groups and with longer follow-ups are under way.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
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14
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Tajiri K, Shimizu Y. Unsolved problems and future perspectives of hepatitis B virus vaccination. World J Gastroenterol 2015; 21:7074-7083. [PMID: 26109794 PMCID: PMC4476869 DOI: 10.3748/wjg.v21.i23.7074] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 03/23/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total eradication, several countries, including Japan, have not yet adopted universal vaccination programs. Some individuals are non-responders to HBV vaccine and several mechanisms responsible for their poor response have been proposed. To overcome non-response, third generation vaccines with pre-S proteins have been developed. These vaccines have shown better anti-HBs responses and may also be effective in preventing infection by HBV with S mutant. Improvement of vaccine efficacy by intradermal administration, or co-administration with cytokines or adjuvants, may also be effective in non-responders. The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
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15
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Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Factors affecting effectiveness of vaccination against hepatitis B virus in hemodialysis patients. World J Gastroenterol 2014; 20:12018-12025. [PMID: 25232238 PMCID: PMC4161789 DOI: 10.3748/wjg.v20.i34.12018] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/29/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is a major global health problem. Despite the success of the general measures against blood transmitted infections in hemodialysis (HD) units, the prevalence of HBV infection among the HD patients is still high. Thus vaccination against HBV is indicating in this population. However, compared with the general population the seroprotection achieved in HD patients remains relatively low, at about 70%. In this review patient, HD procedure and vaccine-associated factors that affect the efficacy of HBV vaccination are analyzed. Also alternative routes of HBV vaccine administration as well as new and more immunogenic vaccine formulations are discussed. However, besides scientific progress, vigilance of HD physicians and staff regarding the general measures against the transmission of blood borne infections and the vaccination against HBV is also required for reducing the prevalence of this viral infection.
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16
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Lankarani KB, Talebzadeh M, Eshraghian A, Malek-Hosseini SA. Granulocyte colony stimulating factor adjuvant role on the immunological response to hepatitis B vaccine in patients with cirrhosis: a double blind randomized placebo controlled trial. HEPATITIS MONTHLY 2014; 14:e15447. [PMID: 24910704 PMCID: PMC4030266 DOI: 10.5812/hepatmon.15447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 12/31/2013] [Accepted: 04/04/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND Patients with liver cirrhosis have usually poor antibody response to hepatitis B virus (HBV) vaccination. OBJECTIVES This study aimed to investigate the effect of granulocyte colony stimulating factor (G-CSF) on increasing antibody titers, after HBV vaccination, in patients with liver cirrhosis waiting for transplantation. PATIENTS AND METHODS From 56 patients with cirrhosis, 28 patients were allocated to receive double dose HBV vaccine (40 μgr) plus G-CSF and 28 patients were allocated to receive double dose HBV vaccine (40 μgr) plus placebo. Injections were performed on weeks 0, 4 and 8 and the blood samples were obtained one month after each vaccination session. RESULTS There was no statistically significant difference between anti-HBV antibody titers in patients receiving double dose HBV vaccination plus G-CSF and patients receiving double dose HBV vaccination plus placebo, after first, second or third vaccination rounds (P > 0.05). Although the adjuvant G-CSF injection did not cause significant increased antibody titers in our patients compared to the placebo group, the increase in antibody titers following vaccination, happened faster in this group, compared to the placebo group. CONCLUSIONS The present study showed that G-CSF is not superior to placebo in production of protective antibody titers after HBV vaccination but could result in a more rapid antibody response, compared to the placebo.
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Affiliation(s)
| | - Mozaffar Talebzadeh
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Ahad Eshraghian
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding Author: Ahad Eshraghian, Department of Internal Medicine, Namazi Hospital, Shiraz University of Medical Sciences, P. O. Box: 71345-1744, Shiraz, IR Iran. Tel: +98-7116125600, E-mail:
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17
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Mathew R, Mason D, Kennedy JS. Vaccination issues in patients with chronic kidney disease. Expert Rev Vaccines 2014; 13:285-98. [PMID: 24405403 DOI: 10.1586/14760584.2014.874950] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Infections are an important cause of morbidity and mortality among patients at all stages of chronic kidney disease. Prevention through vaccination remains the best strategy to minimize the adverse consequences associated with these infectious diseases in this, and all, populations. Unfortunately, patients with chronic kidney disease demonstrate inadequacies of specific immune-cell function that are required for generating a protective vaccine response. Nevertheless, early vaccination of this high-risk population has demonstrated good clinical outcomes during progression to late-stage disease. We review the available evidence linking immune impairment in adult patients with late-stage chronic kidney disease to diminished vaccine responses. We highlight the importance of early vaccination in disease with high risk for development of CKD and novel vaccine approaches in development that may help to address improvement in protective boosting of immunity during late-stage disease.
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Affiliation(s)
- Roy Mathew
- Department of Medicine, Division of Nephrology, Stratton VA Medical Center, Albany, NY, USA
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18
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Soni R, Horowitz B, Unruh M. Immunization in end-stage renal disease: opportunity to improve outcomes. Semin Dial 2013; 26:416-26. [PMID: 23751048 DOI: 10.1111/sdi.12101] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infection is the second most common cause of death in patients with end-stage renal disease (ESRD), following cardiovascular causes. Immunization is a fairly simple, but underutilized, strategy for prevention of infectious morbidity and mortality in patients with kidney failure. It is imperative for nephrologists and primary care providers to have an understanding of immunization as an essential component of preventive healthcare measures in this high-risk population. Patients with ESRD represent a unique population due to their immunosuppressed state, dialysis-related exposures and suboptimal response to routine vaccines. While the Advisory Committee on Immunization Practices (ACIP) provides guidelines for vaccination of patients with renal disease against Hepatitis B, influenza and pneumococcal disease, the data on immunization against other commonly preventable infectious diseases are lacking. This article reviews the recent evidence on immunization in the ESRD population and synthesizes the related implications for maximizing prevention of infectious diseases in this high-risk population.
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Affiliation(s)
- Ritu Soni
- Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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19
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Mahboobi N, Tabatabaei SV, Blum HE, Alavian SM. Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature. Transpl Infect Dis 2012; 14:445-451. [PMID: 22970743 DOI: 10.1111/j.1399-3062.2012.00782.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Revised: 01/08/2012] [Accepted: 04/26/2012] [Indexed: 01/03/2025]
Abstract
BACKGROUNDS AND AIMS Organ shortage is a major problem in transplantation. The use of organs from hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive donors could significantly increase the donor pool. However, little information is available about the impact of HBcAb status of renal donors on viral transmission to recipients. To address this issue, the present quantitative review of relevant studies has been performed. MATERIALS AND METHODS Electronic databases including Medline, EMBASE, ISI, and Scopus were systematically searched for studies that evaluated risk of hepatitis B virus (HBV) transmission through renal transplantation from HBsAg-/HBcAb+ donors. Eligible studies were identified according to predefined criteria. The final outcome was one of HBV markers seroconversion defined as HBsAg, hepatitis B surface antibody (HBsAb), or HBcAb detection in previously seronegative end-stage renal disease (ESRD) patients after transplantation, and without other identified major sources of infection. RESULTS Nine studies with 1385 eligible kidney recipients were included. In total, 45 subjects showed seroconversion of HBV markers as follows: HBsAg (n = 4) (0.28%; 95% confidence interval [CI] 0.006; 0.57), HBcAb (n = 32), HBsAb (n = 5), and either HBcAb or HBsAb (n = 4). The total rate of seroconversion after renal transplantation was calculated to be 3.24% (95% CI: 2.31-4.18). CONCLUSION Our review indicates that the risk of HBV transmission from HBcAb-positive kidney donors is extremely low. Therefore, kidneys from these donors can be transplanted safely into ESRD patients.
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20
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Somi MH, Hajipour B. Improving hepatitis B vaccine efficacy in end-stage renal diseases patients and role of adjuvants. ISRN GASTROENTEROLOGY 2012; 2012:960413. [PMID: 23029621 PMCID: PMC3458294 DOI: 10.5402/2012/960413] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Accepted: 08/01/2012] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) infection is a serious global health problem.The prevalence of viral hepatitis is higher in dialysis patients than in the general population because of the opportunity for exposure during the dialysis procedure. Immunization is the most effective way to prevent transmission of hepatitis B virus (HBV) and hence the development of acute or chronic hepatitis B. It is well established that patients with end-stage renal disease including dialysis-dependent patients, have an impaired immune response to hepatitis B vaccine. End stage renal diseases (ESRD) patients have lower seroconversion rates compared with the subjects with intact renal function. Moreover, even after the completion of vaccination schedule anti-hepatitis B (anti-HBs) titers of responder dialysis, patients are low and decline logarithmically with time. The impaired efficacy of HBV vaccine in patients with ESRD has been attributed to numerous factors such as immune compromise because of uremia and some other factors. One approach to improve the immunogenicity of existing HBV vaccines is adjuvantation, and it's very important to find more effective adjutants for improving HBV vaccine efficacy. In this paper we have a brief review on recently known new ways for improving HBV vaccine efficacy.
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Affiliation(s)
- Mohammad Hossein Somi
- Liver and Gastroenterology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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21
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Abstract
As life expectancy continues to rise, elderly adults represent a rapidly growing proportion of the population. The likelihood of complications of acute and chronic liver disease and overall mortality are higher in elderly populations. Several physiological changes associated with aging, greater prevalence of co-morbid conditions, and cumulative exposure to hepatotropic viruses and environmental hepatotoxins may contribute to worse outcomes of viral hepatitis in the elderly. Although pharmacotherapy for hepatitis B and C continues to evolve, the efficacy, tolerability, and side effects of these agents have not been studied extensively in elderly adults. Immunization against hepatitis A and B in naïve elderly adults is an important public health intervention that needs to be revised and broadened.
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22
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Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood 2012; 119:3383-93. [PMID: 22323450 DOI: 10.1182/blood-2011-11-370130] [Citation(s) in RCA: 256] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Because of their limited lifespan, continuous replenishment of DC is required. Whereas the importance of GM-CSF in regulating DC homeostasis has long been underestimated, this cytokine is currently considered a critical factor for DC development under both steady-state and inflammatory conditions. Regulation of cellular actions by GM-CSF depends on the activation of intracellular signaling modules, including JAK/STAT, MAPK, PI3K, and canonical NF-κB. By directing the activity of transcription factors and other cellular effector proteins, these pathways influence differentiation, survival and/or proliferation of uncommitted hematopoietic progenitors, and DC subset–specific precursors, thereby contributing to specific aspects of DC subset development. The specific intracellular events resulting from GM-CSF–induced signaling provide a molecular explanation for GM-CSF–dependent subset distribution as well as clues to the specific characteristics and functions of GM-CSF–differentiated DCs compared with DCs generated by fms-related tyrosine kinase 3 ligand. This knowledge can be used to identify therapeutic targets to improve GM-CSF–dependent DC-based strategies to regulate immunity.
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23
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Bailey RR, Stuckey DR, Norman BA, Duggan AP, Bacon KM, Connor DL, Lee I, Muder RR, Lee BY. Economic value of dispensing home-based preoperative chlorhexidine bathing cloths to prevent surgical site infection. Infect Control Hosp Epidemiol 2011; 32:465-71. [PMID: 21515977 DOI: 10.1086/659763] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To estimate the economic value of dispensing preoperative home-based chlorhexidine bathing cloth kits to orthopedic patients to prevent surgical site infection (SSI). METHODS A stochastic decision-analytic computer simulation model was developed from the hospital's perspective depicting the decision of whether to dispense the kits preoperatively to orthopedic patients. We varied patient age, cloth cost, SSI-attributable excess length of stay, cost per bed-day, patient compliance with the regimen, and cloth antimicrobial efficacy to determine which variables were the most significant drivers of the model's outcomes. RESULTS When all other variables remained at baseline and cloth efficacy was at least 50%, patient compliance only had to be half of baseline (baseline mean, 15.3%; range, 8.23%-20.0%) for chlorhexidine cloths to remain the dominant strategy (ie, less costly and providing better health outcomes). When cloth efficacy fell to 10%, 1.5 times the baseline bathing compliance also afforded dominance of the preoperative bath. CONCLUSIONS The results of our study favor the routine distribution of bathing kits. Even with low patient compliance and cloth efficacy values, distribution of bathing kits is an economically beneficial strategy for the prevention of SSI.
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Affiliation(s)
- Rachel R Bailey
- Public Health Computational and Operations Research Group, University of Pittsburgh, Pittsburgh, 3520 Forbes Avenue, First Floor, Pennsylvania 15213, USA.
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24
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Bowick GC, McAuley AJ. Vaccine and adjuvant design for emerging viruses: mutations, deletions, segments and signaling. Bioeng Bugs 2011; 2:129-35. [PMID: 21637006 PMCID: PMC3225654 DOI: 10.4161/bbug.2.3.15367] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Revised: 03/02/2011] [Accepted: 03/04/2011] [Indexed: 11/19/2022] Open
Abstract
Vaccination is currently the most effective strategy to medically control viral diseases. However, developing vaccines is a long and expensive process, and traditional methods, such as attenuating wild-type viruses by serial passage, may not be suitable for all viruses and may lead to vaccine safety considerations, particularly in the case of the vaccination of particular patient groups, such as the immunocompromised and the elderly. In particular, developing vaccines against emerging viral pathogens adds a further level of complexity, as they may only be administered to small groups of people or only in response to a specific event or threat, limiting our ability to study and evaluate responses. In this commentary, we discuss how novel techniques may be used to engineer a new generation of vaccine candidates as we move toward a more targeted vaccine design strategy, driven by our understanding of the mechanisms of viral pathogenesis, attenuation and the signaling events which are required to develop a lasting, protective immunity. We will also briefly discuss the potential future role of vaccine adjuvants, which could be used to bridge the gap between vaccine safety, and lasting immunity from a single vaccination.
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Affiliation(s)
- Gavin C Bowick
- Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA.
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25
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Lee BY, Stalter RM, Bacon KM, Tai JHY, Bailey RR, Zimmer SM, Wagner MM. Cost-effectiveness of adjuvanted versus nonadjuvanted influenza vaccine in adult hemodialysis patients. Am J Kidney Dis 2011; 57:724-32. [PMID: 21396760 DOI: 10.1053/j.ajkd.2010.12.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2010] [Accepted: 12/01/2010] [Indexed: 11/11/2022]
Abstract
BACKGROUND Currently more than 340,000 individuals are receiving long-term hemodialysis (HD) therapy for end-stage renal disease and therefore are particularly vulnerable to influenza, prone to more severe influenza outcomes, and less likely to achieve seroprotection from standard influenza vaccines. Influenza vaccine adjuvants, chemical or biologic compounds added to a vaccine to boost the elicited immunologic response, may help overcome this problem. STUDY DESIGN Economic stochastic decision analytic simulation model. SETTING & PARTICIPANTS US adult HD population. MODEL, PERSPECTIVE, & TIMEFRAME The model simulated the decision to use either an adjuvanted or nonadjuvanted vaccine, assumed the societal perspective, and represented a single influenza season, or 1 year. INTERVENTION Adjuvanted influenza vaccine at different adjuvant costs and efficacies. Sensitivity analyses explored the impact of varying influenza clinical attack rate, influenza hospitalization rate, and influenza-related mortality. OUTCOMES Incremental cost-effectiveness ratio of adjuvanted influenza vaccine (vs nonadjuvanted) with effectiveness measured in quality-adjusted life-years. RESULTS Adjuvanted influenza vaccine would be cost-effective (incremental cost-effectiveness ratio <$50,000/quality-adjusted life-year) at a $1 adjuvant cost (on top of the standard vaccine cost) when adjuvant efficacy (in overcoming the difference between influenza vaccine response in HD patients and healthy adults) ≥60% and economically dominant (provides both cost savings and health benefits) when the $1 adjuvant's efficacy is 100%. A $2 adjuvant would be cost-effective if adjuvant efficacy was 100%. LIMITATIONS All models are simplifications of real life and cannot capture all possible factors and outcomes. CONCLUSIONS Adjuvanted influenza vaccine with adjuvant cost ≤$2 could be a cost-effective strategy in a standard influenza season depending on the potency of the adjuvant.
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Affiliation(s)
- Bruce Y Lee
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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26
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Abstract
Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20 years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.
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Affiliation(s)
- M Cornberg
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany.
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27
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Fabrizi F, Dixit V, Messa P, Martin P. Meta-analysis: levamisole improves the immune response to hepatitis B vaccine in dialysis patients. Aliment Pharmacol Ther 2010; 32:756-62. [PMID: 20662784 DOI: 10.1111/j.1365-2036.2010.04410.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients undergoing maintenance dialysis often fail to mount protective antibodies to hepatitis B virus surface antigen (HBsAg) following vaccination against hepatitis B virus (HBV). Some authors have suggested that levamisole improves immune response to HBV vaccine in dialysis population. However, consistent information on this issue does not exist. AIM To evaluate efficacy and safety of levamisole as adjuvant to hepatitis B virus (HBV) vaccine in dialysis patients by performing a systematic review of the literature with a meta-analysis of clinical trials. METHODS We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. Only trials comparing the seroresponse rate in study subjects (levamisole plus HBV vaccine) vs. controls (HBV vaccine alone) were included. The end point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule in study vs. control groups. RESULTS We identified four studies involving 328 unique patients on regular dialysis. Only prospective, randomized clinical trials (RCTs) were included. Pooling of study results showed a significant increase in response rates among study (levamisole plus HBV vaccine) vs. control (HBV vaccine alone) patients; the pooled Odds Ratio was 2.432 (95% Confidence Intervals, 1.34; 4.403), P = 0.002. No study heterogeneity was found. These results did not change in various subgroups of interest. CONCLUSIONS Our meta-analysis showed that levamisole significantly improves immune response to hepatitis B vaccine in dialysis population. The limited number of patients precluded more conclusions.
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Affiliation(s)
- F Fabrizi
- Maggiore Hospital, IRCCS Foundation, Milano, Italy.
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28
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Abstract
The incidence of hepatitis B virus (HBV) infection in dialysis populations has declined over recent decades, largely because of improvements in infection control and widespread implementation of HBV vaccination. Regardless, outbreaks of infection continue to occur in dialysis units, and prevalence rates remain unacceptably high. For a variety of reasons, dialysis patients are at increased risk of acquiring HBV. They also demonstrate different disease manifestations compared with healthy individuals and are more likely to progress to chronic carriage. This paper will review the epidemiology, modes of transmission and diagnosis of HBV in this population. Prevention and treatment will be discussed, with a specific focus on strategies to improve vaccination response, new therapeutic options and selection of patients for therapy.
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Affiliation(s)
- Matthew Edey
- Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia
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29
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Effects of oral levamisole as an adjuvant to hepatitis B vaccine in adults with end-stage renal disease: a meta-analysis of controlled clinical trials. Clin Ther 2010; 32:1-10. [PMID: 20171406 DOI: 10.1016/j.clinthera.2010.01.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2009] [Indexed: 12/14/2022]
Abstract
BACKGROUND Many patients receiving long-term dialysis do not produce protective antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) after HBV vaccination. The results from several studies have suggested benefit of oral levamisole as an adjuvant to HBV vaccination in patients with end-stage renal disease (ESRD). However, reliable information is still lacking. OBJECTIVE This meta-analysis assessed the efficacy and safety profile of oral levamisole as an adjuvant to HBV vaccine in patients with ESRD. METHODS This meta-analysis included prospective controlled clinical trials identified using literature searches of MEDLINE, SCOPUS, Institute for Scientific Information bibliographic database, and Cochrane Collaboration's Central Register of Controlled Clinical Trials for controlled clinical trials that weighted the seroprotection rate in patients with ESRD who received oral levamisole + HBV vaccine versus those who received the HBV vaccine alone (control). The fixed-effects Mantel-Haenszel model was applied with the heterogeneity and sensitivity analyses. The response rate, defined as the proportion of patients with seroprotective concentrations of antibodies to HBsAg (>10 mIU/mL) at completion and 6 to 10 months after completion of the HBV vaccine schedule, was the end point of interest and was also analyzed separately. For the tolerability assessment, studies that reported dose reduction, levamisole discontinuation, and their adverse effects including laboratory abnormalities were included. RESULTS The literature search identified 4 studies that fulfilled the inclusion criteria (328 patients). The mean ages of the patients in these studies ranged from 41 to 53 years, and sex distribution ranged from 52.6% to 68.0% male. Twenty-two patients received oral levamisole 100 mg/d for 12 days (from 6 days before to 6 days after each vaccination). A total of 106 patients received oral levamisole 80 to 120 mg for 4 to 6 months. Aggregation of study results suggested a significant increase in response rate in the group that received levamisole + HBV vaccine compared with the control group (pooled odds ratio [OR] = 2.77 [95% CI, 1.56-4.94]) after completion and 6 to 10 months after the vaccination period (pooled OR = 3.96 [95% CI, 1.71-9.18]). The test of heterogeneity was not statistically significant in either group. Five patients underwent dose reduction due to mild adverse events. In one trial, 3 patients died, 1 of whom was receiving levamisole; however, the authors did not provide the causes of death. No other serious adverse events were reported with levamisole administration. CONCLUSION The results from this meta-analysis suggest significant benefit in the administration of levamisole as an adjuvant to HBV vaccine to increase seroprotection in patients with ESRD.
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The effect of diabetes mellitus on immunological response to hepatitis B virus vaccine in individuals with chronic kidney disease: A meta-analysis of current literature. Vaccine 2010; 28:3773-7. [DOI: 10.1016/j.vaccine.2010.03.038] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2009] [Revised: 02/26/2010] [Accepted: 03/21/2010] [Indexed: 12/20/2022]
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Roukens AH, Vossen AC, Boland GJ, Verduyn W, van Dissel JT, Visser LG. Intradermal hepatitis B vaccination in non-responders after topical application of imiquimod (Aldara). Vaccine 2010; 28:4288-93. [PMID: 20433806 DOI: 10.1016/j.vaccine.2010.04.029] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2010] [Revised: 04/07/2010] [Accepted: 04/13/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND Five to ten percent of immunocompetent persons fail to develop a protective immune response to hepatitis B vaccination, and are defined non-responders (NR). We investigated the immune response to intradermal hepatitis B vaccination after pre-treatment of the skin with the TLR7 agonist imiquimod. METHODS Twenty-one non-responders (anti-HBs <10 IU/l after at least 6 intramuscular hepatitis B vaccinations) were randomly assigned to the control group (N=11) or the experimental group (N=10). Participants in both groups received 3 intradermal (ID) vaccinations with 5 microg HBsAg (0.125 mL) at 0, 1 and 6 months. In the experimental group, the dermal site of injection was pre-treated with 250 mg imiquimod ointment. Anti-HBs antibodies were determined at 0, 1, 2, 6 and 7 months. RESULTS In both study groups, 70% of the participants developed a protective immune response (anti-HBs >or=10 IU/l), after the 3rd intradermal vaccination. CONCLUSION The application of imiquimod on the skin prior to intradermal vaccination did not enhance the humoral response to hepatitis B vaccine. However, irrespective of imiquimod application, 70% of the NR who had not responded to 6 previous intramuscular vaccinations, developed a protective immune response with high affinity antibodies after 3 ID hepatitis B vaccinations with 5 microg HBsAg.
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Affiliation(s)
- Anna H Roukens
- Department of Infectious Diseases, Leiden University Medical Center, The Netherlands.
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Moheno P, Morrey J, Fuchs D. Effect of dipterinyl calcium pentahydrate on hepatitis B virus replication in transgenic mice. J Transl Med 2010; 8:32. [PMID: 20356392 PMCID: PMC2853516 DOI: 10.1186/1479-5876-8-32] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2009] [Accepted: 03/31/2010] [Indexed: 12/26/2022] Open
Abstract
Background Dipterinyl calcium pentahydrate (DCP) has previously been shown to inhibit MDA-MB-231 human breast cancer xenographs in nude mice in a manner correlated with increases in plasma IL-12 and IL-4 concentrations, and decreases in plasma IL-6 levels. DCP also inhibits indoleamine 2,3-dioxygenase (IDO), an immuno-inhibitory enzyme, in human PBMCs (Peripheral Blood Mononuclear Cells). Methods In the present study, DCP was administered per os, once daily for 14 days to hepatitis B virus (HBV) transgenic mice at 23, 7.3, and 2.3 mg/(kg d). Multivariate stepwise regression and MANOVA analyses, by gender and treatment, of liver HBV DNA and RNA measures, liver core and serum HBe antigen assays, serum cytokine/chemokine profiles, and IDO metabolite measurements were performed. Results DCP caused a significant dose-response reduction of log liver HBV DNA as measured by PCR in the female HBV mice. The gender dependence of the anti-HBV DNA activity was explained by the DCP Effects Model (DCP-EM) (p = .001) which includes three serum biomarker changes caused by DCP: 1) decreased MCP-1; 2) decreased Kyn/Trp (an estimation of IDO activity); and 3) increased GM-CSF. Conclusions Immunomodulation via IDO or TDO (tryptophan 2,3-dioxygenase) pathways, along with serum MCP-1 and GM-CSF are proposed to play roles in the anti-HBV mechanism of DCP based upon their coordinated modulation in the reduction of viral DNA replication in HBV mice.
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Affiliation(s)
- Phillip Moheno
- SanRx Pharmaceuticals, Inc,, 603 Colima Street, La Jolla, California 92037-8032, USA.
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Tanwar S, Thursz M. Granulocyte colony-stimulating factor as a novel adjunct to improve hepatitis B vaccination. World J Hepatol 2010; 2:136-8. [PMID: 21160984 PMCID: PMC2999275 DOI: 10.4254/wjh.v2.i3.136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2009] [Revised: 01/18/2010] [Accepted: 01/25/2010] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B vaccination is successful in 95% of individuals. In the remainder, despite repeated attempts, immunization often remains unsuccessful. 'Non-response' leaves the individual susceptible to infection. Various strategies have been employed to overcome this. These include the use of adjuncts alongside conventional vaccines which activate immune responses. In this case report we demonstrate the successful use of the hematopoietic growth factor Granulocyte colony-stimulating factor (G-CSF) as a vaccine adjunct in an individual who had previously failed conventional vaccination three times. The patient tolerated the regimen without any side effects and achieved a hepatitis B surface antibody titer greater than 100 IU/L. Use of G-CSF as a vaccine adjunct for hepatitis B has not previously been reported and the outcome in this case suggests that the use of G-CSF in this context warrants further exploration.
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Affiliation(s)
- Sudeep Tanwar
- Sudeep Tanwar, Mark Thursz, Department of Hepatology, Imperial College London, St Mary's Hospital, Praed Steet, London W2 1NY, United Kingdom
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Chow KM, Lo SHK, Szeto CC, Yuen SK, Wong KS, Kwan BCH, Leung CB, Li PKT. Extra-high-dose hepatitis B vaccination does not confer longer serological protection in peritoneal dialysis patients: a randomized controlled trial. Nephrol Dial Transplant 2010; 25:2303-9. [PMID: 20185409 DOI: 10.1093/ndt/gfq094] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The response to recombinant hepatitis B vaccine remains suboptimal among the dialysis population. METHODS In this multi-centre randomized controlled trial, we studied the factors that modify the response to intramuscular Engerix-B vaccination in patients on peritoneal dialysis. The primary aim was to study if a three-dose schedule of extra-high dose (80 microg) of Engerix-B would offer better primary seroconversion and more persistent serological protection than the conventional 40-microg dose. RESULTS Forty-two peritoneal dialysis patients were randomized to receive the conventional 40-microg Engerix-B dose and 45 patients to 80-microg dose. Seroconversion [hepatitis B surface antibody (anti-HBs) level > or =10 IU/l 3 months after completion of the third dose] occurred in 78.6% of patients after 40-microg Engerix-B dosage treatment versus 62.2% for those receiving 80-microg Engerix-B treatment (P = 0.11). After 12 months, the persistence of protective anti-HBs also did not differ between 40- (45.2%) and 80-microg (51.1%) treatment groups (P = 0.67). In contrast, patients with seroconversion 3 months after the third dose of Engerix-B had a higher normalized protein nitrogen appearance (nPNA) than patients without seroconversion (1.16 +/- 0.25 versus 0.96 +/- 0.23 g/kg/day, P = 0.001). Conclusions. We found no evidence of a worthwhile clinical benefit from increasing the three-dose intramuscular Engerix-B vaccine from 40- to 80-microg dose. An unplanned analysis suggested a role of improved protein intake to improve the immune response to hepatitis B vaccine in peritoneal dialysis patients.
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Affiliation(s)
- Kai Ming Chow
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
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Abstract
The activity of several potent adjuvants, including incomplete Freund's adjuvant, CpG oligodeoxynucleotides, and alum, has been shown to be due at least in part to the induction of cytokines, including type I interferons (IFNs), IFN-gamma, interleukin-2 (IL-2), and IL-12, that play key roles in the regulation of innate and adaptive immunity. The relatively short half-life of recombinant homologues of cytokines has limited their use as vaccine adjuvants. These difficulties have been overcome by encapsulation into liposomes and the use of cytokine expression vectors co-administered with DNA vaccines. Although a number of cytokines including IFN-alpha, IFN-gamma, IL-2, IL-12, IL-15, IL-18, IL-21, GM-CSF, and Flt-3 ligand have been shown to potentiate the immune response to vaccination in various experimental models, the full potential of cytokines as vaccine adjuvants remains to be established.
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Grammatikos AP, Mantadakis E, Falagas ME. Meta-analyses on Pediatric Infections and Vaccines. Infect Dis Clin North Am 2009; 23:431-57. [DOI: 10.1016/j.idc.2009.01.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Molino C, Fabbian F, Cozzolino M, Longhini C. The management of viral hepatitis in CKD patients: an unresolved problem. Int J Artif Organs 2008; 31:683-696. [PMID: 18825641 DOI: 10.1177/039139880803100802] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Chronic kidney disease (CKD) patients in dialysis (HD) show peculiar, atypical features of clinical presentation and diseases (cardiovascular, metabolic, hematologic). This is also true for viral hepatitis infections, for which CKD patients represent an important risk group. In the past, hepatitis B virus (HBV) was the major cause of viral hepatitis in end-stage renal disease (ESRD). However, the introduction of a rigorous infection-control strategy, routine screening of patients and staff for hepatitis B serologic markers, vaccination of susceptible patients and staff, use of separate rooms and dedicated machines for HD of HbsAg-positive patients have all led to a decline in the spread of HBV infection in dialysis. Despite the prevalence of the antibody-hepatitis C virus (HCV), there has been a marked decrease in HD patients; after the introduction of routine screening for HCV and the use of erythropoietin, its occurrence ranges from 5% to 25% in the United States, with a prevalence of 6.8% in Europe. In CKD and in HD patients, the presence of HBV and HCV is an independent and significant risk factor for death and this risk may be at least partially attributed to chronic liver disease with its attendant complications. Liver disease can progress with modest hepatic inflammation and prominent fibrosis; the natural history of viral hepatitis in these patients is dependent on the immune dysfunction typical of kidney disease. Despite recent advances in antiviral therapy, there are still many uncertainties in regards to the efficacy and long-term outcomes of treatment with antiviral agents.
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Affiliation(s)
- C Molino
- Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy.
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