Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants

Guillaume Butler‐Laporte; Kathryn Auckland; Zannatun Noor; Mamun Kabir; Masud Alam; Tommy Carstensen; Genevieve L. Wojcik; Amanda Yoon-Yee Chong; Cristina Pomilla; Janelle Annette Noble; Shana L. McDevitt; Gaby P. Smits; Susan Wareing; Fiona R.M. van der Klis; Katie JM Jeffery; Beth D. Kirkpatrick; Sodiomon Bienvenu Sirima; Shabir Ahmed Madhi; Alison M. Elliott; John Brent Richards; Adrian V. S. Hill; Priya Duggal; PROVIDE authors; Cryptosporidiosis Birth Cohort authors; Manjinder Singh Sandhu; Rashidul Haque; William A. Petri; Alexander J. Mentzer

doi:10.1101/2023.06.26.23291885

Genetic & Genomic MedicinemedRxivJun 26, 2023

Preprint

Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants

Guillaume Butler‐Laporte iD, Kathryn Auckland iD, Zannatun Noor iD, Mamun Kabir iD, Masud Alam iD, Tommy Carstensen iD, Genevieve L. Wojcik iD, Amanda Yoon-Yee Chong iD, Cristina Pomilla iD, Janelle Annette Noble iD, Shana L. McDevitt iD, Gaby P. Smits iD, Susan Wareing iD, Fiona R.M. van der Klis iD, Katie JM Jeffery iD, Beth D. Kirkpatrick iD, Sodiomon Bienvenu Sirima iD, Shabir Ahmed Madhi iD, Alison M. Elliott iD, John Brent Richards iD, Adrian V. S. Hill iD, Priya Duggal iD, PROVIDE authors, Cryptosporidiosis Birth Cohort authors, Manjinder Singh Sandhu iD, , Alexander J. Mentzer iD

Abstract

Hepatitis 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 individuals DPB1*04:01 was associated with higher HBV antibody responses (p=4.5x10-30). 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.

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