Molecular analysis of the a determinant of HBsAg in children of HBeAg-positive mothers upon failure of postexposure prophylaxis.

ABSTRACT

OBJECTIVE: To investigate the a determinant of hepatitis B virus (HBV) S gene for the presence of mutations responsible for vaccine failure. METHODS: The a determinant of HBV S gene was amplified in sera obtained from 11 HBV-positive infants and children born to asymptomatic HBeAg-positive mothers by nested polymerase chain reaction (PCR) and subsequently subjected to direct sequencing. The sequences obtained were translated into the corresponding amino acids and compared to amino acid sequences of HBV subtype adr. All infants under investigation had received recombinant hepatitis B vaccine within 24 hours after delivery and had completed the recommended vaccination course, consisting of three to four doses administered at defined intervals. RESULTS: The usual divergence regarding genotype and subtype was identified among the 11 samples tested. Only two exhibited a point mutation within the a determinant, one of which consisted of a substitution of glycine with alanine at position 145, and the other of a substitution of glutamine with arginine at position 129. CONCLUSION: Eleven neonates were positive for HBV infection, and two of them showed point mutations that might have rendered the virus resistant to the vaccine, possibly due to a change in the S protein's secondary structure. Yet, this remains a matter of speculation, since the other seven cases positive for hepatitis B viral DNA merely demonstrated the usual genotype and subtype. The presence of escape mutants of HBV can be considered rather negligible with respect to vaccination programs, especially as the vaccine has been shown to reduce hepatitis B, as well as hepatocellular carcinoma efficiently.