S Gene Variations Of Hepatitis B Virus In Children With Vaccination Failure

Obejective: To determine variations of “major hydrophilic region” and “a determinant region” in S gene of hepatitis B virus in children with vaccine immunized failure.Methods: Serum samples from HBV vaccine immunized failure child and non-immunized child were collected; HBV S gene was amplified by nest PCR, sequenced, genome-typing by tools and compared with the consensus sequence of different genotype HBV genomes.Results: Nucleotide mutation ratio of “a determinant region” in CHB patients with vaccine immunized failure was obviously higher than that of vaccine navie patients(31.7% vs. 10%, P=0.044). Vaccine immunized failure patients with mutation in MHR or a determinant had a obviously lower viral DNA loading compared with that of mutation free patients(MHR: log10 6.9 ± 1.8 vs. log10 7.7 ± 1.8, P=0.000; a determinant: log10 7.1±1.6 vs. log10 7.6±1.9, P=0.000). In addition, vaccine immunized failure patients with MHR mutation also had higher ALT value(67.1±58.8 vs. 56.5±51.8, P=0.018). Totally 145 amino acid variation types were detected in vaccine immunized failure patients, including several “hot mutations”: I110L(6), K122R(15), T126A(18), I126T(14), M133L(7), G145R(6) and Y161F(12). Patients with G145 R and Y161 F had obviously lower serum viral loading(log10 6.8±1.1 vs. log10 7.5±1.8, P=0.048; log10 5.0±2.6 vs log10 7.3±1.8, P=0.000, respectively).Conclusion: In general, vaccine immunized failure children have a higher mutation rate in MHR region and a determinant region, which correlate with lower viral loading and higher ALT value.