Persistence of HBsAg-specific antibodies and immune memory two to three decades after hepatitis B vaccination in adults

Pierre Van Damme, Marc Dionne, Geert Leroux-Roels, Olivier Van Der Meeren, Emmanuel Di Paolo, Bruno Salaun, Pemmaraju Surya Kiran, Nicolas Folschweiller, Pierre Van Damme, Marc Dionne, Geert Leroux-Roels, Olivier Van Der Meeren, Emmanuel Di Paolo, Bruno Salaun, Pemmaraju Surya Kiran, Nicolas Folschweiller

Abstract

The duration of protection after hepatitis B vaccination is not exactly known. This phase IV study evaluated antibody persistence and immune memory 20-30 years after adult immunization with recombinant hepatitis B vaccine (HBsAg vaccine, Engerix-B) in routine clinical practice. Men and women 40-60 years old, with documented evidence of vaccination with three or four HBsAg vaccine doses 20-30 years earlier and without subsequent booster, were enrolled and received HBsAg vaccine as challenge dose. HBsAg-specific antibodies (anti-HBs) and frequencies of HBsAg-specific circulating memory B cells and CD4+ T cells expressing combinations of activation markers (CD40L, IL2, IFNγ, TNFα) were measured prechallenge, 7 and 30 days postchallenge. Of 101 participants in the according-to-protocol cohort for immunogenicity, 90.1% had anti-HBs concentrations ≥ 10 mIU/mL prechallenge administration; 84.2% and 100% mounted an anamnestic response 7 and 30 days postchallenge, respectively. HBsAg-specific memory B and CD4+ T cells expressing at least two activation markers were low prechallenge and increased markedly postchallenge. These results suggest sustained immune memory and long-term protection 20-30 years after a complete primary HBsAg vaccination course during adulthood, in line with current recommendations that a booster is not needed in fully vaccinated immunocompetent adults.

Trial registration: ClinicalTrials.gov NCT02901951.

Keywords: HBsAg; anamnestic response; hepatitis B vaccine; immune memory; persistence.

Conflict of interest statement

OVDM, EDP, BS, PS and NF are employees of the GSK group of companies; OVDM, EDP, BS and NF own shares in the GSK group of companies; and the institutions of PVD, MD and GLR received grants from the GSK group of companies to conduct the study.

© 2019 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Reverse cumulative distribution curves of anti‐HBs concentrations before, 7 and 30 days after the challenge dose (ATP cohort for immunogenicity). Anti‐HBs, antibodies against hepatitis B surface antigen; ATP, according‐to‐protocol
Figure 2
Figure 2
Anti‐HBs concentrations 7 days (A) and 30 days (B) postchallenge as a function of prechallenge concentrations, with regression line (ATP cohort for immunogenicity). Anti‐HBs, antibodies against hepatitis B surface antigen; ATP, according‐to‐protocol
Figure 3
Figure 3
Frequencies of HBsAg‐specific IgG‐producing memory B cells per million of IgG‐producing memory B cells (A) and of HBsAg‐specific CD4+ T cells expressing a combination of at least two activation markers (among CD40L, IL2, IFNγ and TNFα) per million of CD4+ T cells (B) (ATP cohort for immunogenicity). HBsAg, hepatitis B surface antigen; IgG, immunoglobulin G; CD40L, CD40 ligand; IL2, interleukin 2; IFNγ, interferon gamma; TNFα, tumour necrosis factor alpha; ATP, according‐to‐protocol; N, number of participants with available results; Q1‐Q3, interquartile range. The x symbols in the boxes depict geometric mean frequencies
Figure 4
Figure 4
Summary of the research, its clinical relevance and impact on public health

References

    1. World Health Organization . Global Hepatitis Report. 2017; . Accessed 25 April, 2018.
    1. The Polaris Observatory Collaborators . Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3:383‐403.
    1. World Health Organization . Disease burden and mortality estimates: Summary tables of mortality estimates by cause, age and sex, globally and by region, 2000‐2015. . Accessed 25 April, 2018.
    1. Hyams KC. Risks of chronicity following acute hepatitis B virus infection: a review. Clin Infect Dis. 1995;20:992‐1000.
    1. World Health Organization . Hepatitis B vaccines: WHO position paper ‐ July 2017. Wkly Epidemiol Rec. 2017;92:369‐392.
    1. Meireles LC, Marinho RT, Van Damme P. Three decades of hepatitis B control with vaccination. World J Hepatol. 2015;7:2127‐2132.
    1. Wiesen E, Diorditsa S, Li X. Progress towards hepatitis B prevention through vaccination in the Western Pacific, 1990‐2014. Vaccine. 2016;34:2855‐2862.
    1. Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine. 2008;26:6266‐6273.
    1. Kao JH. Hepatitis B vaccination and prevention of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol. 2015;29:907‐917.
    1. World Health Organization . Meeting of the Strategic Advisory Group of Experts on immunization, October 2016 ‐ conclusions and recommendations. Wkly Epidemiol Rec. 2016;91:561‐582.
    1. World Health Organization . Meeting of the Strategic Advisory Group of Experts on immunization, October 2016 ‐ evidence to recommendations table. 2016; . Accessed 25 April, 2018.
    1. European Consensus Group on Hepatitis B Immunity . Are booster immunisations needed for lifelong hepatitis B immunity? Lancet. 2000;355:561‐565.
    1. Van Damme P. Long‐term protection after hepatitis B vaccine. J Infect Dis. 2016;214:1‐3.
    1. Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis. 2011;53:68‐75.
    1. Brunskole Hummel I, Zitzmann A, Erl M, Wenzel JJ, Jilg W. Characteristics of immune memory 10‐15 years after primary hepatitis B vaccination. Vaccine. 2016;34:636‐642.
    1. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546‐1555.
    1. Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489‐492.
    1. Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010;17:1055‐1065.
    1. West DJ, Calandra GB. Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination. Vaccine. 1996;14:1019‐1027.
    1. Crotty S, Aubert RD, Glidewell J, Ahmed R. Tracking human antigen‐specific memory B cells: a sensitive and generalized ELISPOT system. J Immunol Methods. 2004;286:111‐122.
    1. Leroux‐Roels G, Marchant A, Levy J, et al. Impact of adjuvants on CD4(+) T cell and B cell responses to a protein antigen vaccine: results from a phase II, randomized, multicenter trial. Clin Immunol. 2016;169:16‐27.
    1. Cunningham AL, Heineman TC, Lal H, et al. Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older. J Infect Dis. 2018;217:1750‐1760.
    1. Van Damme P, Leroux‐Roels G, Suryakiran P, Folschweiller N, Van Der Meeren O. Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine. Hum Vaccin Immunother. 2017;13:972‐980.
    1. McMahon BJ, Dentinger CM, Bruden D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 22‐year follow‐up study and response to a booster dose. J Infect Dis. 2009;200:1390‐1396.
    1. Bruce MG, Bruden D, Hurlburt D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 30‐year follow‐up study and response to a booster dose. J Infect Dis. 2016;214:16‐22.
    1. Gara N, Abdalla A, Rivera E, et al. Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults. Clin Infect Dis. 2015;60:505‐513.
    1. Poovorawan Y, Chongsrisawat V, Theamboonlers A, Bock HL, Leyssen M, Jacquet JM. Persistence of antibodies and immune memory to hepatitis B vaccine 20 years after infant vaccination in Thailand. Vaccine. 2010;28:730‐736.
    1. Poovorawan Y, Chongsrisawat V, Theamboonlers A, Crasta PD, Messier M, Hardt K. Long‐term anti‐HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response: a 20‐year follow‐up study in Thailand. Hum Vaccin Immunother. 2013;9:1679‐1684.
    1. Poovorawan Y, Chongsrisawat V, Theamboonlers A, Leroux‐Roels G, Crasta PD, Hardt K. Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. Hum Vaccin Immunother. 2012;8:896‐904.
    1. Gilca V, De Serres G, Boulianne N, 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;31:448‐451.
    1. Van Den Ende C, Marano C, Van Ahee A, Bunge EM, De Moerlooze L. The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience. Expert Rev Vaccines. 2017;16:811‐832.
    1. Yang S, Tian G, Cui Y, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep. 2016;6:27251.
    1. Amanna IJ, Carlson NE, Slifka MK. Duration of humoral immunity to common viral and vaccine antigens. N Engl J Med. 2007;357:1903‐1915.
    1. Buisman AM, de Rond CG, Ozturk K, Ten Hulscher HI, van Binnendijk RS. Long‐term presence of memory B‐cells specific for different vaccine components. Vaccine. 2009;28:179‐186.
    1. Simons BC, Spradling PR, Bruden DJ, et al. A longitudinal hepatitis B vaccine cohort demonstrates long‐lasting hepatitis B virus (HBV) cellular immunity despite loss of antibody against HBV surface antigen. J Infect Dis. 2016;214:273‐280.
    1. Werner JM, Abdalla A, Gara N, Ghany MG, Rehermann B. The hepatitis B vaccine protects re‐exposed health care workers, but does not provide sterilizing immunity. Gastroenterology. 2013;145:1026‐1034.
    1. Bauer T, Jilg W. Hepatitis B surface antigen‐specific T and B cell memory in individuals who had lost protective antibodies after hepatitis B vaccination. Vaccine. 2006;24:572‐577.
    1. Chinchai T, Chirathaworn C, Praianantathavorn K, et al. Long‐term humoral and cellular immune response to hepatitis B vaccine in high‐risk children 18‐20 years after neonatal immunization. Viral Immunol. 2009;22:125‐130.
    1. Lu CY, Ni YH, Chiang BL, et al. Humoral and cellular immune responses to a hepatitis B vaccine booster 15‐18 years after neonatal immunization. J Infect Dis. 2008;197:1419‐1426.
    1. Saffar H, Saffar MJ, Ajami A, Khalilian AR, Shams‐Esfandabad K, Mirabi AM. Long‐term T‐cell‐mediated immunologic memory to hepatitis B vaccine in young adults following neonatal vaccination. Hepat Mon. 2014;14:e22223.
    1. Centers for Disease Control and Prevention . Interpretation of Hepatitis B serologic test results. . Accessed 25 April, 2018.
    1. Centers for Disease Control and Prevention . Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991;40:1‐25.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir