Long-term protection of neonatal hepatitis B vaccination in a 30-year cohort in Hong Kong
Authors: Ada Wai-chi Lin, Ka-hing Wong
Journal: Journal of Hepatology (2013)

Universal neonatal hepatitis B (HB) vaccination programme is effective in the control of hepatitis B virus (HBV) infection in countries with different endemicity [1Ni Y.H. Chang M.H. Wu J.F. Hsu H.Y. Chen H.L. Chen D.S. Minimization of hepatitis B infection by a 25-year universal vaccination programme.J Hepatol. 2012; 57: 730-735Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 2Boccalini S. Taddei C. Ceccherini V. Bechini A. Levi M. Bartolozzi D. et al.Economic analysis of the first 20 y of universal hepatitis B vaccination program in Italy: an a posteriori evaluation and forecast of future benefits.Hum Vaccin Immunother. 2013; 9Google Scholar]. However, the long-term protective effect of neonatal hepatitis B vaccination into adulthood, especially in endemic areas and to subjects with high risk of infection, remains uncertain [[3]Wu T.W. Lin H.H. Wang L.Y. Chronic hepatitis B infection in adolescents who received primary infantile vaccination.Hepatology. 2013; 57: 37-45Crossref PubMed Scopus (70) Google Scholar]. Universal neonatal HB vaccination programme has been introduced in Hong Kong, a region of moderate to high endemicity of hepatitis B, since 1988. To study the long-term effect of neonatal HB vaccination in those with high risk of HBV infection in Hong Kong, we evaluated the serial changes of HBV serological markers over a 30-year period in a cohort born to hepatitis B carrier mothers and who received neonatal hepatitis B vaccination. In 1983, 1112 neonates, born to hepatitis B carrier mothers in a public hospital in Hong Kong, were recruited for a study to evaluate the response of passive–active hepatitis B vaccination with hepatitis B immunoglobulin and three-dose regimen of hepatitis B vaccines of three different schedules: conventional (0, 1, and 6 months), delayed (2, 3, and 8 months), and accelerated (0, 1, and 2 months) [[4]Young B.W. Lee S.S. Lim W.L. Yeoh E.K. The long-term efficacy of plasma-derived hepatitis B vaccine in babies born to carrier mothers.J Viral Hepat. 2003; 10: 23-30Crossref PubMed Scopus (37) Google Scholar]. HBV serological markers, including HBsAg, antibody to surface antigen (anti-HBs) and antibody to core-antigen (anti-HBc), were determined upon completion of vaccination and at subsequent intervals up to 30 years of follow-up. Anti-HBs positivity was defined as anti-HBs level higher or equal than 10 IU/L. Anti-HBc seroconversion was defined as anti-HBc positivity for two consecutive readings measured at or after the 2nd year. Upon completion of the three-dose vaccination, 1006 (92.6%) out of 1086 subjects developed anti-HBs positivity. Thirty-nine subjects failed the vaccination and developed chronic HBV infection, giving the HBsAg positivity rate of 3.5%. Thirty-five (89.7%) of them were born to mothers who were also hepatitis B e-antigen (HBeAg) positive. All of these 39 subjects were tested HBsAg positive before the age of two, with no new infection found at subsequent follow-up time points of years 3, 5, 7, 10, 13, 16, 21, 25, and 30 post-vaccination (Table 1). At the 30th year of follow-up, the anti-HBs positivity rate fell to 37.4%. There were no differences in the development of HBsAg and anti-HBs positivity between subjects receiving three different vaccination schedules (p >0.05). Ninety-seven subjects developed anti-HBc seroconversion over the 30-year period, giving a rate of 9% (39 subjects tested for HBsAg positive were excluded), with no statistically significant difference in anti-HBs positive and negative subjects (9.3% vs. 5%, p >0.05).Table 1Temporal change of hepatitis B virus serological markers in the study cohort over 30 years.#Upon completion of a 3-dose vaccination.∗Excluded 39 subjects who developed HBsAg positivity.∗∗Based on one anti-HBc result. Open table in a new tab #Upon completion of a 3-dose vaccination. ∗Excluded 39 subjects who developed HBsAg positivity. ∗∗Based on one anti-HBc result. We described the first study showing long-term protective effect of neonatal HB vaccination into a cohort up to 30 years of follow-up. While most studies reported in the literature measured immune-protection by detectable levels of antibodies to HBV [5Gabbuti A. Romano L. Blanc P. Meacci F. Amendola A. Mele A. et al.Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian health adolescents.Vaccine. 2007; 25: 3129-3132Crossref PubMed Scopus (91) Google Scholar, 6Alfaleh F. Alshehri S. Alansari S. Aljeffri M. Almazrou Y. Shaffi A. et al.Long-term protection of hepatitis B vaccine 18 years after vaccination.J Infect. 2008; 57: 404-409Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar], this study provided direct evidence of effective protection in subjects with high risk of infection, both via perinatal route or close interpersonal contact with their infected mothers and possibly other infected household members at childhood. Among 97 subjects who developed anti-HBc seroconversion, a majority (43%) of these seroconversions occurred at or before year two. On the other hand, with such a long follow-up period up to 30 years, this study also demonstrated the protective effect of vaccine into adulthood, when the subjects might be exposed to horizontal transmission of HBV, notably from sexual contact. Despite the dropping rate of anti-HBs and new occurrence of anti-HBc seroconversion over the years, there was no new development of HBsAg positivity after the first two years in the entire follow-up period. Our findings were in line with other studies which suggested long-term protection of HB vaccine albeit with shorter follow-up durations. Persistence of serum protective antibody level was shown in older children or adolescents who received vaccination at infancy [6Alfaleh F. Alshehri S. Alansari S. Aljeffri M. Almazrou Y. Shaffi A. et al.Long-term protection of hepatitis B vaccine 18 years after vaccination.J Infect. 2008; 57: 404-409Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 7Aypak C. Yüce A. Yıkılkan H. Görpelioğlu S. Persistence of protection of hepatitis B vaccine and response to booster immunization in 2- to 12-year-old children.Eur J Pediatr. 2012; 171: 1761-1766Crossref PubMed Scopus (13) Google Scholar, 8McMahon B.J. Bruden D.L. Petersen K.M. Bulkow L.R. Parkinson A.J. Nainan O. et al.Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up.Ann Intern Med. 2005; 142: 333-341Crossref PubMed Scopus (262) Google Scholar]. Moreover, anamnestic response was demonstrated in those who had lost protective antibody level, years after vaccination [[9]Chaves S.S. Fischer G. Groeger J. Patel P.R. Thompson N.D. Teshale E.H. et al.Persistence of long-term immunity to hepatitis B among adolescents immunized at birth.Vaccine. 2012; 30: 1644-1649Crossref PubMed Scopus (49) Google Scholar]. A recent study further suggested that, apart from a protective serum antibody level, cellular immune response might also play a role for protection against HBV after vaccination [[10]Carollo M. Palazzo R. Bianco M. Pandolfi E. Chionne P. Fedele G. et al.Hepatitis B specific T cell immunity induced by primary vaccination persists independently of the protective serum antibody level.Vaccine. 2013; 31: 506-513Crossref PubMed Scopus (41) Google Scholar]. There were two limitations in this study. First, subjects who were not followed-up might have affected the overall representativeness of the data. At the 30th year of follow-up, 246 (22.1%) subjects returned for serological tests. 372 (33.5%) subjects defaulted follow-up, and 492 (44.2%) subjects were lost to follow-up. Two subjects died in the study period but neither of them was known to be HB carrier. Second, the cohort received three different vaccination schedules that different response to three vaccination schedules could not be totally excluded. In conclusion, this study demonstrated direct long-term efficacy of neonatal HB vaccination in a high-risk cohort, up to 30 years in an endemic region. The implementation of universal neonatal HB vaccination in Hong Kong since 1988 is likely to remain effective for long-term prevention of HBV infection in the territory in the absence of a policy of booster in the adolescent or early adult population. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The authors would like to thank Dr Janice Lo and her colleagues of Public Health Laboratory Services Branch, Department of Health, for the laboratory support, and Ms Monica Lo of Special Preventive Programme, Department of Health, for the statistical support.