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.
曹阳, 贺晓烨, 李雯莉, 高冉冉, 王莹. 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[J]. 河北医学, 2022, 28(9): 1473-1479.
CAO Yang, et al. Characterization of Hepatitis B Virus/S-Gene Mutation and Its Association with Immune Escape of Hepatitis B Vaccine. HeBei Med, 2022, 28(9): 1473-1479.
[1] 李嘉铃,董柏青,苏永健,等.MicroRNA基因单核苷酸多态性和DNA甲基化与儿童乙型肝炎疫苗无或低免疫应答的关联性[J].中国疫苗和免疫,2021,27(4):370-376. [2] Tang Y,Liu X,Lu X,et al.Occult hepatitis B virus infection in maintenance hemodialysis patients:prevalence and mutations in "a" determinant[J].Int Med Sci,2020,17(15):2299-2305. [3] 邓中凤,陈萍,邹杨.隐匿性乙型肝炎病毒感染血液透析患者的分子特性及转归[J].肾脏病与透析肾移植杂志,2020,29(4):328-332. [4] Lazarevic I,Banko A,Miljanovic D,et al.Immune-escape hepatitis B virus mutations associated with viral reactivation upon immunosuppression[J].Viruses,2019,11(9):778. [5] 中华人民共和国卫生部.预防接种工作规范[M].北京:人民卫生出版社,2005:6-7. [6] 杜红飞,庞雪利,阳燕,等.乙肝肝硬化早期患者外周血环状RNA差异表达谱的研究[J].成都医学院学报,2020,15(3):314-319. [7] 顾红芳,梁晓华,邓雪莲.乙型肝炎病毒PreS/S基因突变的研究进展[J].中国输血杂志,2020,33(1):89-93. [8] 赵鸿.丙氨酸转氨酶正常慢性乙型肝炎病毒感染者启动抗病毒治疗的恰当指标[J].中华肝脏病杂志,2021,29(9):883-884. [9] An epidemiological survey of HBV infection and low-level HBsAg in military camps in eastern China:Erratum.Medicine (Baltimore)[J].2019,98(4):e14273. [10] 吴明山,刘振球,陈兴栋,等.全球乙型肝炎病毒基因型的分布现状[J].中华疾病控制杂志,2020,24(2):217-221. [11] Huang Y,Wang B,Peng Z,et al.Hepatitis B virus surface gene mutants in immunoprophylaxis-failed infants from southern China[J].Med Virol,2019,91(6):1069-1075. [12] Colagrossi L,Hermans LE,Salpini R,et al.Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe[J].BMC Infect Dis,2018,18(1):251.
2022, Vol. 28 
冀公网安备13080202000677号