Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants

Abstract

AbstractHepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individualsDPB1*04:01was associated with higher HBV antibody responses (p=4.5×10−30). The underlying mechanism is a result of higher affinity binding of HBV surface antigen epitopes to DPB1*04:01 dimers. This is likely a result of evolutionary pressure at the HBV surface antigen ‘a-determinant’ segment incurring VEM specific to HBV. Prioritizing pre-S isoform HBV vaccines may tackle the rise of HBV vaccine evasion.One-Sentence SummaryHost genetics underlying hepatitis B vaccine response in Bangladeshi infants identifies mechanisms of viral vaccine escape, and how to prevent it.