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

Abstract

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. We evaluated the frequency, genotype, and global distribution of polymorphisms at sites associated with vaccine escape in 4244 unique full‐length HBV genomes. The “a” determinant within the Surface gene was inspected for polymorphisms at sites identified previously associated with vaccine escape. Nearly, 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. Among 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. 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.

Detection of Q129H Immune Escape Mutation in Apparently Healthy Hepatitis B Virus Carriers in Southwestern Nigeria

“…The IEMs were detected in the HBV sequences of samples from six apparently healthy prospective blood donors in Ekiti and two pregnant women each from Ekiti and Ondo States, Nigeria. All sequences obtained in this study were classified as HBV genotype E, which is known to show a clear genotypic divergence from all genotypes within the a determinant, where escape mutations can occur [ 27 , 28 ], reported that the types of polymorphisms at positions associated with escape mutations observed in HBV vary from one genotype to another and that the most common of these polymorphisms found in genotype E are T116N, P120L/S, Q129H/R, M133I, D144E, and G145I. Different studies report the presence of the Q129H mutation in different HBV genotypes, including genotype E [ 29 , 30 , 31 ], whereas the escape mutation Q129R has been detected in genotypes A, C, and D and Q129L in genotype F only.…”

Endemic hepatitis B virus (HBV) among hospital in-patients in Bangladesh, including evidence of occult infection

“…VEMs are most commonly reported within the HBV surface antigen (HBsAg) ‘a’ determinant (residues 124-147), which is the target of neutralising antibodies. We therefore focused scrutiny on this region, searching for evidence of polymorphisms Q129H/R, M133L, F/Y134I/L/T, K141E, P142S and G145R/A that have been highlighted by a recent paper taking a systematic approach to the identification of VEMs in global data 47 . We also added A128V to this list, as this has been independently reported as a VEM in Bangladesh 48,49 .…”

Endemic HBV among hospital in-patients in Bangladesh, including evidence of occult infection

“…VEMs are most commonly reported within the HBV surface antigen (HBsAg) 'a' determinant (residues 124-147), which is the major target of neutralising antibodies. We therefore focused scrutiny on this region, searching for evidence of previously catalogued polymorphisms Q129H/R, M133L, F/Y134I/L/T, K141E, P142S and G145R/A [34]. We also added A128V, as this has been independently reported as a VEM in Bangladesh [35,36].…”

“…Our study identified HBV infection in Bangladeshi adults, with a prevalence of 8 % in a tertiary hospital cohort, of which 3/16 (18.8 %) were OBI. Existing sequence data from Bangladesh suggest genotypes C and D each account for ~40 % of the total burden, and genotype A for the remainder, with a Four full-length HBV consensus sequences generated in this study were analysed alongside HBV genotype reference sequences (for genotypes A-J) 34 and 61 sequences originating from Bangladesh identified in online databases (unlabelled branches, Table S2). Genotype A sequences are highlighted in blue, genotype C in red and genotype D in yellow.…”

“…Phylogenetic tree to show the relationship between new HBV sequences and published HBV sequences from Bangladesh. Four full-length HBV consensus sequences generated in this study were analysed alongside HBV genotype reference sequences (for genotypes A-J)34 and 61 sequences originating from Bangladesh identified in online databases (unlabelled branches, TableS2). Genotype A sequences are highlighted in blue, genotype C in red and genotype D in yellow.…”