Mutational Analysis of HBs Ag-Positive Mothers and Their Infected Children despite Immunoprophylaxis

Abstract

Hepatitis B vaccination is safe and effective, although breakthrough infection occasionally occurs in those who receive the vaccine and hepatitis B immunoglobulin (HBIg) prophylaxis. Sequence variation in their antigenic regions is one of the most powerful strategies that are used by viruses to escape recognition by B and T cell-mediated immune responses. The aim of this study was to explore the mutational profile of HBV in vertical transmission. Six HBsAg-positive mothers and their children who developed HBV infection despite immunoprophylaxis were enrolled. After extraction of HBV DNA from sera, the full HBV genome or surface gene was amplified by Gunther and hemi-nested PCR, respectively. After sequencing, the mutational analysis on paired samples between mothers and children were carried out and compared. Different mutations were found in four children; at least, one arose in functional and/or immune epitope activities. Of 30 amino acid changes, 11 (36.6%) were located within the known HBV immune epitopes. In three children, mutations occurred within the “a” determinant region, one mutation (B2) was identical to the mother of patient, an indication of vertical transmission. The other two (B4 and B5) were considered as vaccine escape mutations. Three children harbored wild-type HBsAg, similar to their mothers. Regarding transmission in infected children, the immunoprophylaxis had no effect and failure of vaccination was observed in 2 isolates. These findings emphasized the need for an alternative regimen, such as the administration of boosters or a more effective HBV vaccine for high-risk children who are born to HBsAg-positive mothers.

Keywords

• HBV escape mutants
• HBV prophylaxis
• Hepatitis B immunoglobulin