乙型肝炎病毒/S型区变异特征及其与乙肝疫苗免疫逃逸的研究

doi:10.3969/j.issn.1006-6233.2022.09.013

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Abstract Objective: To study the characteristics of hepatitis B virus (HBV) S-gene mutation and its association with immune escape of hepatitis B vaccine. Methods: 1,973 inpatients in the hospital between March 2021 and March 2022 were selected as samples for a cross-sectional study.All patients completed hepatitis B (HepB) vaccination according to the standard procedures of 0,1 month and 6 months.HBV serum markers and HBV S-gene mutation were detected. Results: There were 47 HBsAg positive samples among 1973 patients (2.38%),the rate of HBsAg positivity was higher in those aged >18 years than in those aged 1-18 years,and the rate of HBsAg positivity was lower in those with HBV-negative parents than in those with HBV-positive mothers,all with statistically significant differences (P<0.05).Compared with the standard sequence,162 nucleotide mutation sites and 98 amino acid mutation sites were detected in 47 HBsAg-positive samples,among which the mutation sites in the a determinant (aa124-147) mainly included I/T126A/N/I/S,Q129H/R,M133L,K141E,T143S,D144A/EH and G145R/A,mutation sites in the a determinant upstream (aa99-123) were mainly Q101R/H,L110I,G112K,S113T/G,S117G and P120Q/R/L,and mutation sites in the a determinant downstream (aa148-169) mainly included Y161F/C,E164D,F161Y and R160K.Among 47 HBsAg-positive samples,30 samples were found to have amino acid mutation with the detection of 63.83%,among which 19 had amino acid polarity change (according for 63.33%) and 11 occurred in the a determinant (aa124-147),including 5 mutation sites of T126I,Q129R,T143S,D144A and G145A. Conclusion: HBV S-gene mutation is closely associated to the immune escape of HepB vaccine.The mutation sites of T126I,Q129R,T143S,D144A and G145A in the a determinant (aa124-147) can cause changes in the polarity and hydrophilicity of HBsAg,resulting in the decrease of antigenicity and the occurrence of immune escape.

Key words： Hepatitis B virus Vaccine Immune escape Gene mutation A determinant Antigenicity

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.09.013 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I9/1473

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