PATTERNS OF CIRCULATING HEPATITIS-B SURFACE-ANTIGEN VARIANTS AMONG VACCINATED CHILDREN BORN TO HEPATITIS-B SURFACE-ANTIGEN CARRIER AND NON-CARRIER MOTHERS - A POPULATION-BASED COMPARATIVE-STUDY

Hepatitis B virus (HBV) variants that possessed missense mutation with in the neutralization epitope of the major S antigen as defined by ami no acid residues (aa#) 124-147, termed the 'a' determinant variants, w ere identified through a population-based serosurvey of 2,305 children of the vaccinated birth cohorts born after 1986. Data on the 678 nucl eotides encoding the S antigen of HBV were available for 75 HBV strain s that were collected from 63 vaccinated children and 12 unvaccinated or incompletely vaccinated children, and 21 HBV strains from 25 unvacc inated adults. Among the diverse patterns of one to three amino acid s ubstitutions within the 'a' determinant, 145-Arg occurred most frequen tly (5/14); other variants were: 126-Ala, 127-Thr, 126-Ser/131-Asn/133 -Thr, 129-His, 129-Arg, 123-Asn/131-Ile, 133-Leu, 141-Glu, and 141-Arg /144-Ala. Only one of these variants occurred in the 16 hepatitis B su rface antigen (HBsAg)-carrier children born to HBsAg-negative mothers, whereas 12 of these variants occurred in the 20 (50%) children born t o HBsAg-positive mothers. In addition, early administration of HBV vac cine within the noenatal period increased the likelihood of the emerge nce of these variants to 64.7% (11/17). Five of the 21 (23.8%) unvacci nated HBsAg-carrier adults harbored the 'a' determinant variants posse ssing mutations within aa# 125-136, i.e. the putative first loop forme d by the cysteine disulfide bonds. Vaccinated children were likely to harbor HBV variants possessing mutations involving altered charge of s ide chains and/or its hydrophobicity of amino acid residues within the putative second loop between aa#140 and 146. Our data suggest that em ergence of these HBV S gene mutants in the phase of HBV vaccination pr ogram would be most common among populations in whom perinatal/vertica l transmission of HBV is most common, i.e. southeast Asian and the Tai wanese.