Molecular evolution of hepatitis B vaccine escape variants in China, during 2000–2016

•Genotype C HBV vaccine escape strains were more diversity than genotype B HBV.•Genotype B HBV vaccine escape strains evolved more rapidly than genotype C HBV.•Genotype C HBV vaccine escape populations fluctuated more than genotype B HBV.•The positive selected mutations outside MHR but related with antigenicity circulated in China. Hepatitis B vaccine escape variants are the main threat to hepatitis B virus (HBV) infection in vaccination era worldwide. With 215 genotype B HBV and 313 genotype C HBV vaccine escape variants isolated from China during 2000–2016, we reported that genotype B HBV vaccine escape strains diverged in ∼1997 (95% HPD; 1987–2005), while genotype C HBV vaccine escape strains diverged in ∼1976 (95% HPD; 1955–2003). Additionally, the p-distance of genotype C HBV vaccine escape strains was 0.0291±0.0169, which was significantly higher than that in the genotype B HBV (t=131.02, p