The distribution of hepatitis B virus surface antigen polymorphisms at positions associated with vaccine escape

Abstract

Background Hepatitis B virus (HBV) infects over 250 million people worldwide. Vaccination is effective at preventing infection, although several mutations within the ‘a’ determinant region of the HBV surface antigen (HBsAg) are associated with vaccine escape. Methods We evaluated the frequency, genotype, and global distribution of polymorphisms at sites associated with vaccine escape in 4,244 unique full‐length HBV genomes. The ‘a’ determinant within the Surface gene was inspected for polymorphisms at sites identified previously associated with vaccine escape. Results 268 (6.3%) sequences from 36 countries contained a polymorphism at a site associated with vaccine escape including 22 genotype A, 99 genotype B, 93 genotype C, 32 genotype D, 14 genotype E, 3 genotype F, 2 genotype G, and 3 genotype I. In genotype A, the most common polymorphism occurred at M133. In genotype B, Q129 and M133 occurred 45 and 51 times, respectively, accounting for 94% of polymorphisms. Polymorphisms at G145 were most frequent in genotype C, while P120 was most common in genotype D. Amongst all genotypes, polymorphisms at M133 were the most common and accounted for 30.9% of polymorphisms. Polymorphisms at T116, P120, F134, K141, and P142 occurred in geographically diverse locations, whereas polymorphisms at Q129, M133, D144, and G145 were concentrated in East Asia. Conclusion While the sample size is large, this approach relied on convenience sampling within each country, and many countries have no data available, thereby highlighting the need for additional routine surveillance of surface antigen mutations associated with vaccine escape.