Analysis of HBsAg mutations in the 25 years after the implementation of the hepatitis B vaccination plan in China


Since 1992, China has promoted hepatitis B vaccination. Concurrently, during this period, increasing use of immunoglobulins and nucleoside analogues might have exerted selective pressure on the hepatitis B virus (HBV) S gene, driving mutations in the HBsAg and changed the subtype. Using the National Center for Biotechnology Information database, we obtained gene sequence information for HBV strains from China and analysed changes in HBsAg subtypes and substitution mutations in HBsAg in 5-year intervals over 25 years to identify potential challenges to the prevention and treatment of hepatitis B. Most HBV sequences from China were genotype C (1996/2833, 70.46%) or B (706/2833, 24.92%). During the implementation of hepatitis B vaccination (recombinant hepatitis B vaccine was subgenotype A2 and HBsAg subtype adw2), the proportion of subtypes ayw1 and adw3 in genotype B and ayw2 in genotype C increased over the programme period. The overall mutation rate in HBsAg tended to decrease for genotype B, whereas, for genotype C, the rate increased gradually and then decreased slightly. Moreover, the mutation rate at some HBsAg amino acid sites (such as sG145 of genotype B and sG130 and sK141 of genotype C) is gradually increasing. HBV strains with internal stop codons of HBsAg (e.g., sC69*) and additional N-glycosylation (e.g., sG130N) mutations should be studied extensively to prevent them from becoming dominant circulating strains. The development of HBV vaccines and antiviral immunoglobulins and use of antiviral drugs may require making corresponding changes.

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Data availability

The datasets generated and analyzed during this study are available with the corresponding author, on reasonable request.


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This work was supported by grants from the Fujian Provincial Health and Family Planning Research Talents Training Project (No. 2018-2-67) and Xiamen Municipal Health and Family Planning Commission. Authors have no conflicting interests to declare relevant to this study. We thank Ms. Bihuan Che for her kindly technical support.

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HY and JT conceived of and designed the study; HY, XF, JT, YW, and ZL performed the research; HY, XF, and JT analyzed the data; and XF wrote the paper.

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Correspondence to Xiaochun Fu.

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Ye, H., Teng, J., Lin, Z. et al. Analysis of HBsAg mutations in the 25 years after the implementation of the hepatitis B vaccination plan in China. Virus Genes (2020).

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  • Hepatitis B virus
  • Vaccine
  • Mutation rate
  • Stop codon
  • N-glycosylation