Changes of hepatitis B surface antigen variants in carrier children beforeand after universal vaccination in Taiwan

Mutants of a determinant of hepatitis B surface antigen (HBsAg) identified in vaccinated children pose a potential threat to long-term success of vacc ination programs. We examined the mutants of a determinant (residues 110-16 0) of HBsAg in hepatitis B virus (HBV) DNA-positive children identified dur ing previous serosurveys in Taipei undertaken just before (1984), 5 years a fter (1989), and 10 years after (1994) universal vaccination began. In HBV DNA-positive children from 3 surveys, the prevalence of a determinant mutan ts increased from 8 of 103 (7.8%) in 1984 to 10 of 51 (19.6%) in 1989 and 9 of 32 (28.1%) in 1994 and was higher in those fully-vaccinated than unvacc inated (12/33 vs. 15/153, P = .0003). Most amino acid changes of the varian ts clustered in residues 125-129 and 140-149. In all 27 children with detec table mutants, the mean age of those vaccinated was younger than those unva ccinated (4.8 +/- 3.8 vs. 7.9 +/- 2.3 yrs, P < .05); and mutations occurred in a region with greatest local hydrophilicity (residues 140-149) more fre quently in those vaccinated than in those unvaccinated (10/12 vs. 6/15; P = .0253). More mutated residues and more mutations at neutralizing epitopes, such as N146, C147, T148, and C149, were found in the 1994 survey. Vaccina ted children may contract variant infections through vertical or horizontal transmission. Universal vaccination has accelerated an accumulation of HBs Ag a determinant mutants with amino acid changes critical for immune escape in vaccinated children who became carriers, suggesting that new vaccinatio n strategies should be considered.