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. 2016 Jun 7;2016(6):CD008256.
doi: 10.1002/14651858.CD008256.pub3.

Booster dose vaccination for preventing hepatitis B

Jalal Poorolajal  1 , Elham Hooshmand
Affiliations

Booster dose vaccination for preventing hepatitis B

Jalal Poorolajal et al. Cochrane Database Syst Rev. .

Abstract

Background: Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection.

Objectives: To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL.

Search methods: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016).

Selection criteria: Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin.

Data collection and analysis: Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants with anamnestic immune response in non-protected participants and signs of HBV infection. Secondary outcomes were the proportion of participants that developed local and systemic adverse events following a booster dose injection. We planned to report the weighted proportion with 95% confidence intervals (CIs).

Main results: There were no eligible randomised clinical trials fulfilling the inclusion criteria of this review.

Authors' conclusions: We were unable to include any randomised clinical trials on the topic; only randomised clinical trials will be able to provide an answer as to whether a booster dose vaccination is able to protect against hepatitis B infection.

PubMed Disclaimer

Conflict of interest statement

Jalal Poorolajal declares no conflicts of interest. Elham Hooshmand declares no conflicts of interest.

Figures

1
1
NPV: non‐protected vaccinees (with anti‐HBs less than 10 mIU/mL)
 AIR: anamnestic immune response
 * Positive: number with anti‐HBs at or above 10 mIU/mL
 ** Negative: number with anti‐HBs below 10 mIU/mL
2
2
Study flow diagram.
See this image and copyright information in PMC

Update of

References

References to studies excluded from this review

Cassidy 2001 {published data only}
    1. Cassidy WM, Watson B, Ioli VA, Williams K, Bird S, West DJ. A randomized trial of alternative two‐ and three‐dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001;107(4):626‐31. - PubMed
Chan 1991 {published data only}
    1. Chan C‐Y, Lee S‐D, Tsai Y‐T, Lo K‐J. Booster response to recombinant yeast‐derived hepatitis‐B vaccine in vaccinees whose anti‐HBs responses were initially elicited by a plasma‐derived vaccine. Vaccine 1991;9(10):765‐7. - PubMed
Diez‐Domingo 2010 {published data only}
    1. Diez‐Domingo J, Flores SA, Martin JC, Klopfer SO, Schodel FP, Bhuyan PK. A randomized, multicenter, open‐label clinical trial to assess the anamnestic immune response 4 to 8 years after a primary hepatitis B vaccination series. Pediatric Infectious Disease Journal 2010;29(10):972‐4. - PubMed
Gilca 2013 {published data only}
    1. Gilca V, Serres G, Boulianne N, Murphy D, Wals P, Ouakki M, et al. Antibody persistence and the effect of a booster dose given 5, 10 or 15 years after vaccinating preadolescents with a recombinant hepatitis B vaccine. Vaccine 2013;31(3):448‐51. - PubMed
Teoharov 2013 {published data only}
    1. Teoharov P, Kevorkyan A, Petrova N, Baltadzhiev I, Damme P. Immune memory and immune response in children from Bulgaria 5‐15 years after primary hepatitis B vaccination. Pediatric Infectious Disease Journal 2013;32(1):51‐3. - PubMed
Trivello 1995 {published data only}
    1. Trivello R, Chiaramonte M, Ngatchu T, Baldo V, Majori S, Moschen ME, et al. Persistence of anti‐HBs antibodies in health care personnel vaccinated with plasma‐derived hepatitis B vaccine and response to recombinant DNA HB booster vaccine. Vaccine 1995;13(2):139‐41. - PubMed
van der Sande 2007 {published data only}
    1. Sande MA, Waight PA, Mendy M, Zaman S, Kaye S, Sam O, et al. Long‐term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence. Plos One 2007;2(8):e753. - PMC - PubMed
Williams 2001 {published data only}
    1. Williams JL, Christensen CJ, McMahon BJ, Bulkow LR, Cagle HH, Mayers JS, et al. Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers. Vaccine 2001;19(28‐29):4081‐5. - PubMed
Wu 2010 {published data only}
    1. Wu ZH, Cui FQ, Gong XH. Effect analysis on non‐and‐low response infants after revaccinated hepatitis B vaccine. Zhongguo Yi Miao He Mian Yi 2010;16(3):207‐10. - PubMed
Yao 2011 {published data only}
    1. Yao J, Ren J, Shen L, Chen Y, Liang X, Cui F, et al. The effects of booster vaccination of hepatitis B vaccine on anti‐HBV surface antigen negative children 11‐15 years after primary vaccination. Human Vaccines 2011;7(10):1055‐9. - PubMed
Zanettia 2012 {published data only}
    1. Zanettia A, Parlatob A, Romanòa L, Desolec MG, Ferrerad G, Giurdanellae F, et al. Challenge with a hepatitis B vaccine in two cohorts of 4‐7‐year‐old children primed with hexavalent vaccines: an open‐label, randomised trial in Italy. Vaccine 2012;30(39):5770‐5. - PubMed
Zhuang 1998 {published data only}
    1. Zhuang G, Xu H, Zuo H, Wang X, Liu P, Kong L. Six‐year efficacy of hepatitis B revaccination: a double‐blind, placebo‐controlled and randomized field trial. Journal of Xi'an Medical University 1998;10(1):44‐8.

Additional references

Banatvala 2003
    1. Banatvala JE, Damme P. Hepatitis B vaccine – do we need boosters?. Journal of Viral Hepatitis 2003;10:1‐6. - PubMed
Brok 2008
    1. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta‐analyses. Journal of Clinical Epidemiology 2008;61:763‐9. - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analyses may be inconclusive ‐ Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analyses. International Journal of Epidemiology 2009;38(1):287‐98. - PubMed
But 2008
    1. But DYK, Lai CL, Lim WL, Fung J, Wong DKH, Yuen MF. Twenty‐two years follow‐up of a prospective randomized trial of hepatitis B vaccines without booster dose in children: Final report. Vaccine 2008;26:6587‐91. - PubMed
Chen 2005
    1. Chen W, Gluud C. Vaccines for preventing hepatitis B in health‐care workers. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD000100.pub3] - DOI - PubMed
DeMets 1987
    1. DeMets DL. Methods for combining randomized clinical trials: strengths and limitations. Statistics in Medicine 1987;6(3):341‐50. - PubMed
Dentinger 2005
    1. Dentinger CM, McMahon BJ, Butler JC, Dunaway CE, Zanis CL, Bulkow LR, et al. Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth. Pediatric Infectious Disease Journal 2005;24(9):786‐92. - PubMed
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7:177‐88. - PubMed
European Consensus Group 2000
    1. European Consensus Group on Hepatitis B Immunity. Are booster immunizations needed for lifelong hepatitis B immunity?. Lancet 2000;355:561–5. - PubMed
FitzSimons 2005
    1. FitzSimons D, Francois G, Hall A, McMahon B, Meheus A, Zanetti A, et al. Long‐term efficacy of hepatitis B vaccine, booster policy and impact of hepatitis B virus mutants. Vaccine 2005;23:4158‐66. - PubMed
Gamble 2005
    1. Gamble C, Hollis S. Uncertainty method improved on best‐worst case analysis in a binary meta‐analysis. Journal of Clinical Epidemiology 2005;58:579‐88. - PubMed
Gilca 2009
    1. Gilca V, Serres G, Boulianne N, Wals P, Murphy D, Trudeau G, et al. Antibody kinetics among 8‐10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given 5 or 10 years later. Vaccine. 2009; Vol. 27, issue 43:6048‐53. - PubMed
Gluud 2007
    1. Gluud C, Brok J, Gong Y, Koretz RL. Hepatology may have problems with putative surrogate outcome measures. Journal of Hepatology 2007;46(4):734‐42. - PubMed
Gluud 2016
    1. Gluud C, Nikolova D, Klingenberg SL. Cochrane Hepato‐Biliary Group. About Cochrane (Cochrane Review Groups (CRGs)) 2016, Issue 4. Art. No.: LIVER.
Goh 1995
    1. Goh KT, Oon CJ, Heng BH, Lim GK. Long‐term immunogenicity and efficacy of a reduced dose of plasma‐based hepatitis B vaccine in young adults. Bulletin of the World Health Organization 1995;73(4):523‐7. - PMC - PubMed
GRADEpro [Computer program]
    1. Brozek J, Oxman A, Schünemann H. GRADEpro. Version 3.2 for Windows. Grade Working Group 2004‐2007, 2008.
Hadler 1986
    1. Hadler SC, Francis DP, Maynard JE, Thompson SE, Judson FN, Echenberg DF, et al. Long‐term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. New England Journal of Medicine 1986;315(4):209‐14. - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ (Clinical Research Ed.) 2003;327:557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
ICH‐GCP 1997
    1. International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice CFR & ICH Guidelines. Vol. 1, Philadelphia: Barnett International/PAREXEL, 1997.
Jakobsen 2014
    1. Jakobsen JC, Wetterslev J, Winkel P, Lange T, Gluud C. Thresholds for statistical and clinical significance in systematic reviews with meta‐analytic methods. BMC Medical Research Methodology 2014;14(120):1‐13. - PMC - PubMed
John 2005
    1. John TJ, Cooksley G. Hepatitis B vaccine boosters: Is there a clinical need in high endemicity populations?. Journal of Gastroenterology and Hepatology 2005;20:5‐10. - PubMed
Joshi 1995
    1. Joshi N, Kumar YRN, Srinivas DV, Kumar A, Rao PN. Recombinant hepatitis‐B vaccine long‐term efficacy in hospital personnel. Gastroenterology 1995;108(4):A1093.
Lai 1993
    1. Lai CL, Wong BC, Yeoh EK, Lim WL, Chang WK, Lin HJ. Five‐year follow‐up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine vs. plasma‐derived vaccine in children: immunogenicity and anamnestic responses. Hepatology 1993;18(4):763‐7. - PubMed
Lee 2006
    1. Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen‐positive mothers. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD004790.pub2] - DOI - PubMed
Liao 1999
    1. Liao SS, Li RC, Li H, Yang JY, Zeng XJ, Gong J, et al. Long‐term efficacy of plasma‐derived hepatitis B vaccine: a 15‐year follow‐up study among Chinese children. Vaccine 1999;17:2661‐6. - PubMed
Mast 2006
    1. Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR. Morbidity and Mortality Weekly Report 2006;55(RR‐16):1‐33. - PubMed
McMahon 2005
    1. McMahon BJ, Bruden DL, Petersen KM, Bulkow LR, Parkinson AJ, Nainan O, et al. Antibody levels and protection after hepatitis B vaccination: results of a 15‐year follow‐up. Annals of Internal Medicine 2005;142(5):333‐41. - PubMed
Mintai 1993
    1. Mintai Z, Kezhou L, Lieming D, Raymond S. Duration and efficacy of immune response to hepatitis‐B vaccine in high‐risk Chinese adolescents. Clinical Infectious Diseases 1993;16(1):165‐7. - PubMed
Poorolajal 2009a
    1. Poorolajal J, Majdzadeh R. Prevalence of chronic hepatitis B infection in Iran: a review article. Journal of Research in Medical Sciences 2009;14(4):249‐58. - PMC - PubMed
Poorolajal 2009b
    1. Poorolajal J, Mahmoodi M, Majdzadeh R, Haghdoost A, Nasseri‐Moghaddam S, Fotouhi A, et al. Seroprotection of Hepatitis B vaccine and need for booster dose: a meta‐analysis. Hepatitis Monthly 2009;9(4):293‐304. - PubMed
Poorolajal 2010a
    1. Poorolajal J, Mahmoodi M, Haghdoost A, Majdzadeh R, Nasseri‐Moghaddam S, Fotouhi A. Long‐term protection provided by hepatitis B vaccine and need for booster dose: A meta‐analysis. Vaccine 2010;28(3):623‐31. - PubMed
Puro 2005
    1. Puro V, Carli GD, Cicalini S, Soldani F, Balslev U, Begovac J, et al. European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus. Euro Surveillance 2005;10(10):260‐4. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603. - PubMed
Samandari 2007
    1. Samandari T, Fiore AE, Negus S, Williams JL, Kuhnert W, McMahon BJ, et al. Differences in response to a hepatitis B vaccine booster dose amongAlaskan children and adolescents vaccinated during infancy. Pediatrics 2007;120(2):e373‐81. - PubMed
Thorlund 2009
    1. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta‐analyses. International Journal of Epidemiology 2009;38(1):276‐86. - PubMed
Thorlund 2010
    1. Thorlund K, Anema A, Mills E. Interpreting meta‐analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV‐infected individuals. Clinical Epidemiology 2010;2:57‐66. - PMC - PubMed
Thorlund 2011
    1. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for Trial Sequential Analysis (TSA). ctu.dk/tsa/files/tsa_manual.pdf 2011 (accessed 12 May 2016).
TSA 2011 [Computer program]
    1. Copenhagen Trial Unit. TSA ‐ Trial Sequential Analysis. Version 0.9 Beta. Copenhagen: Copenhagen Trial Unit, 2011.
Wainwright 1989
    1. Wainwright RB, McMahon BJ, Bulkow LR, Hall DB, Fitzgerald MA, Harpster AP, et al. Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population. JAMA 1989;261(16):2362‐6. - PubMed
Wainwright 1997
    1. Wainwright RB, Bulkow LR, Parkinson AJ, Zanis C, McMahon BJ. Protection provided by hepatitis B vaccine in a Yupik Eskimo population ‐ Results of a 10‐year study. Journal of Infectious Diseases 1997;175:674‐7. - PubMed
Watson 2001
    1. Watson B, West DJ, Chilkatowsky A, Piercy S, Ioli VA. Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine. Vaccine 2001;19:3164‐8. - PubMed
Wetterslev 2008
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta‐analysis. Journal of Clinical Epidemiology 2008;61(1):64‐75. - PubMed
Wetterslev 2009
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in a random‐effects meta‐analysis. BMC Medical Research Methodology 2009;9:86. - PMC - PubMed
Whittle 2002
    1. Whittle H, Jaffar S, Wansbrough M, Mendy M, Dumpis U, Collinson A, et al. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. BMJ (Clinical Research Ed.) 2002;325:569‐75. - PMC - PubMed
WHO 2001
    1. World Health Organization. Introduction of hepatitis B vaccine into childhood immunization services. www.who.int/immunization/documents/WHO_VB_01.31/en/ 2001 (accessed 11 May 2015).
WHO 2002
    1. World Health Organization. Hepatitis B. www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/ 2002 (accessed 11 May 2015).
WHO 2003
    1. World Health Organization. Expanded program on immunization: measles and hepatitis B. www2.wpro.who.int/rcm/en/archives/rc54/rc_resolutions/wpr_rc54_r03.htm 2003 (accessed 11 May 2015).
Williams 2003
    1. Williams IT, Goldstein ST, Tufa J, Tauillii S, Margolis HS, Mahoney FJ. Long term antibody response to hepatitis B vaccination beginning at birth and to subsequent booster vaccination. Pediatric Infectious Disease Journal 2003;22(2):157‐63. - PubMed
Yuen 1999
    1. Yuen MF, Lim WL, Cheng CC, Lam SK, Lai CL. Twelve‐year follow‐up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine versus plasma‐derived vaccine without booster doses in children. Hepatology 1999;29(3):924‐7. - PubMed
Yuen 2004
    1. Yuen MF, Lim WL, Chan AOO, Wong DKH, Sum SSM, Lai CL. 18‐year follow‐up study of a prospective randomized trial of hepatitis B vaccinations without booster doses in children. Clinical Gastroenterology and Hepatology 2004;2:941‐5. - PubMed
Zhang 1993
    1. Zhang M, Liu K, Jin J, Ding L, Zhou S, Yu Q, et al. Five‐year follow‐up of immune response to hepatitis B vaccine in juveniles. Chinese Medical Journal 1993;106(2):97‐9. - PubMed

References to other published versions of this review

Poorolajal 2010b
    1. Poorolajal J, Mahmoodi M, Haghdoost A, Majdzadeh R, Nasseri‐Moghaddam S, Ghalichi L, et al. Booster dose vaccination for preventing hepatitis B. Cochrane Database of Systematic Reviews 2010, Issue 11. [DOI: 10.1002/14651858.CD008256.pub2] - DOI - PubMed

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