乙肝疫苗母-婴阻断失败者病毒全基因变异分析

Objective To determine the factors responsible for failed postnatal immunoprophylaxis for hepatitis B virus(HBV) in Qidong, China. Methods Eleven children who developed into chronic HBV infection after receiving HBIG and HBV recombinant vaccines were recruited into the study. Eleven paired mothers with chronic hepatitis and other 6 mothers whose children successfully generated anti-HBs after im-munoprophylaxis were included as the control in the study. Full-length HBV DNA was amplified through ser-um sample by PCR method and underwent cloning and sequencing. HBV DNA level was quantified by real-time PCR. Results The mean levels of HBV DNA in mothers who had HBV DNA positive children and healthy children were ( 1.2 ×107± 3.1 × 106 ) copies/ml and ( 1.6× 107±8.8×106 ) copies/ml, respec-tively. There was no significant difference between the groups (P >0.05). Meanwhile, viral load in chil-dren was unrelated to that in their mothers (r2 =0.2429). In 11 HBV DNA positive children, 4(36.4% ) demonstrated amino acid substitutions in HBsAg "a" determinant region with 6 different types, I.e. T125A, I126T, Q129H, M133V, D144V and G145A. All of the mothers showed the wild-type sequence in "a" epitope, indicating surface escape mutants were not acquired from the initial infection, but developed under the immune pressure. The mutation rates after immunoprophylaxis for preS1, preS2, S, X, preC/C and P genes were 0.38%, 0. 22%, 0.27%, 0.17%, 0.11%, and 0.11%, respectively, nt2999-3157 in preS1, nt529-677 in S, nt1955-2016 in C, nt923-1001 and nt2489-2602 in P genes were among the hottest muta-tional spots throughout the HBV genome. Conclusion HBV mutation may occur in all the open readingframes after passive and active immunoprophylaxis. In addition to S gene, HBV preS and P genes could alsoassociate with the escape mutants.

Mutations in hepatitis B virus genome involved in immunoprophylaxis failure against vertical transmission