Failure of neonatal hepatitis B vaccination: the role of HBV-DNA levels in hepatitis B carrier mothers and HLA antigens in neonates

Abstract

In a hepatitis B vaccination program (1982-1992), 705 infants born to HBsAg-positive mothers received HBIg within 2 h of birth and were vaccinated according to a three- or four-dose vaccination schedule, starting either at 3 months or directly after birth. Eight children HBsAg-positive during the first year of life (group 1: infected nonresponders). To determine whether failure of the hepatitis B vaccination was due to perinatal high-level maternal viraemia or genetically determined infant nonresponsiveness to the vaccine, we measured HBsAg and anti-HBs levels in infants and HBeAg and hepatitis B virus-DNA levels in maternal serum, and determined the HLA type of the infants. Controls included 14 infants with a normal anti-HBs response 1 year after vaccination (group 2: noninfected responders) and all eight infants without HBsAg and anti-HBs 1 year after vaccination (group 3: noninfected low responders). HBsAg, HBeAg and anti-HBs were measured by radioimmunoassay (Abbott Laboratories), hepatitis B virus-DNA was measured quantitatively by solution hybridization for groups 1, 2, and 3 (Abbott hepatitis B virus-DNA assay, Abbott Laboratories), and HLA was characterized by microcytotoxicity test for groups 1 and 3. All infants in groups 1 and 2 were born to HBeAg carrier mothers, and those in group 3 to HBeAg-negative mothers. Hepatitis B virus-DNA levels in maternal serum in group 1 were significantly higher than in group 2 (Wilcoxon rank-sum test: p < 0.01). Hepatitis B virus-DNA was not observed in group 3 maternal serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)