Hepatitis B virus Surface gene mutants in immunoprophylaxis-failed infants from Southern China.

Hepatitis B virus (HBV) vaccination was considered the most powerful tool for preventation of HBV transmission from mother to infant. In 1992 a universal HBV vaccination program for infants was lauched in China. The aim of this study was to investigate the HBV Surface antigen (HBsAg) varations in immunoprophylaxis-failed infants, vaccine free infant patients and adult chronic hepatitis B(CHB) patients (without nucleoside analog treatment). Immunoprophylaxis-failed infants were recurited from two centers (Guangdong and Chongqing, representing Southern China). HBV serum markers, including HBsAg, Hepatitis e antigen (HBeAg) and core antigen, were detected by ELISA. HBV DNA load was detected by q-PCR. Nucleotide sequences encoding HBsAg were amplified and analyzed. Frequencies of amino acid substitutions within the second loop of "a" determinant (region with greater local hydrophilicity) in immunoprophylaxis-failed infants were clearly higher than the unvaccinated infant patients and adult CHB patients (9.6% vs 0% vs 3.8%, χ2= 7.454, P=0.024). More than 50% (52.8%) aa substitutions in immunoprophylaxis-failed infants were located in B cell epitopes, while 64.6% aa substitutions in adult CHB patients were located in CTL cell epitopes. HBeAg negative patients had higher substitution frequency in CTL and Th cell epitopes, and in immunoprophylaxis-failed infant patients with substitution in MHR region had higher ALT level (68.6±111.5 vs 62.1±132.2, P=0.026), and lower DNA load (7.03±1.72 vs 7.82±1.73, P<0.001). In conclusion, our results observed vaccine induced immune selection pressure in vaccine failed infants, substitutions in "a" determinant, especially the G145 substitution was still the most stable and remarkable site of vaccine escape. This article is protected by copyright. All rights reserved.