Evidence of protection against clinical and chronic hepatitis B infection 20 years after infant vaccination in a high endemicity region

Abstract

SummaryVaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg −/+ and HBeAg −/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0-1-2-12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti-HBs antibodies and serological markers of hepatitis B infection (anti-HBc, HBsAg, and in selected cases HBeAg, anti-HBe, HBV DNA). During the 20-year follow-up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti-HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti-HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long-term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure. (http://www.clinicaltrials.gov NCT00240500 and NCT00456625)

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…antibody levels decay much more rapidly than expected as well as having a historical prevalence on the low-end of the endemic spectrum (3% vs. 6% in Alaska or 9.8% in China) [9,87]. In highrisk regions, antibody levels may remain high in the population due to natural boosting, where constant re-exposure to HBV would lead to persistent antibody production within the host [99].…”

“…However, studies have shown that over time, protective anti-HBs levels begin to decay, and can become undetectable or reduced below the protective threshold (<10 mIU/ml), when initial vaccine dose is given at birth (and followed commonly by second and third dose within the first year of life) [71,91,99]. The decaying antibody levels have called into question whether or not the three dose vaccine is sufficient in protecting the host, or if a booster dose is required [100].…”

Reply

“…10 The anti-HBc-positive rates of the first decade in children of HBeAg-positive mothers were 9.5% and 14.3%, respectively, for whom with and without booster vaccination was at 5 years of age. 11 For their second decade of life, these rates were 22.2% and 28.6%, respectively. 11 More important, HBV DNA was detected with a high frequency (81 of 106) in a cohort of HBsAg(2)/anti-HBs(1)/anti-HBc(1) young adults who were vaccinated neonatally.…”

Cost-effectiveness Analysis of the National Perinatal Hepatitis B Prevention Program

“…Recent evidence suggests vaccination confers immunity into early adulthood. [35][36][37] This study did not account for infections avoided at later stages in life (eg, during adolescence and adulthood …”