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 Y Chong; Cristina Pomilla; Janelle A Noble; Shana L McDevitt; Gaby Smits; Susan Wareing; Fiona Rm van der Klis; Katie Jeffery; Beth D Kirkpatrick; Sodiomon Sirima; Shabir Madhi; Alison Elliott; J Brent Richards; Adrian Vs Hill; Priya Duggal; PROVIDE authors, Cryptosporidiosis Birth Cohort authors; Manjinder S Sandhu; Rashidul Haque; William A Petri Jr; Alexander J Mentzer

doi:10.1101/2023.06.26.23291885

Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants

medRxiv [Preprint]. 2023 Jun 29:2023.06.26.23291885. doi: 10.1101/2023.06.26.23291885.

Authors

Guillaume Butler-Laporte^{1

2

3}, Kathryn Auckland¹, Zannatun Noor⁴, Mamun Kabir⁴, Masud Alam⁴, Tommy Carstensen^{5

6}, Genevieve L Wojcik⁷, Amanda Y Chong¹, Cristina Pomilla⁵, Janelle A Noble^{8

9}, Shana L McDevitt¹⁰, Gaby Smits¹¹, Susan Wareing¹², Fiona Rm van der Klis¹¹, Katie Jeffery¹², Beth D Kirkpatrick¹³, Sodiomon Sirima¹⁴, Shabir Madhi¹⁵, Alison Elliott^{16

17}, J Brent Richards^{2

18

19

20

21}, Adrian Vs Hill²², Priya Duggal⁷; PROVIDE authors, Cryptosporidiosis Birth Cohort authors; Manjinder S Sandhu²³, Rashidul Haque⁴, William A Petri Jr²⁴, Alexander J Mentzer¹

Affiliations

¹ Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
² Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada.
³ Division of Infectious Diseases, McGill University Health Centre, Montréal, Québec, Canada.
⁴ International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
⁵ Wellcome Trust Sanger Institute, University of Cambridge, Hinxton, United Kingdom.
⁶ Queen Mary University of London, London, United Kingdom.
⁷ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁸ Children's Hospital Oakland Research Institute, Oakland, California, USA.
⁹ Department of Pediatrics, University of California, San Francisco, California, USA.
¹⁰ Media Labs, Inc. Alameda, CA, USA.
¹¹ National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
¹² Microbiology Department, John Radcliffe Hospital, Oxford University NHS Foundation Trust, Oxford, UK.
¹³ Department of Microbiology and Molecular Genetics, Vaccine Testing Center, University of Vermont College of Medicine, Vermont, USA.
¹⁴ Groupe de Recherche Action en Santé (GRAS) 06 BP 10248 Ouagadougou, Burkina Faso.
¹⁵ South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
¹⁷ Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
¹⁸ Department of Human Genetics, McGill University, Montréal, Québec, Canada.
¹⁹ 5 Prime Sciences Inc, Montreal, Quebec, Canada.
²⁰ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada.
²¹ Department of Twin Research, King's College London, London, United Kingdom.
²² The Jenner Institute, University of Oxford, Oxford, United Kingdom.
²³ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom.
²⁴ Department of Medicine, Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

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=4.5×10^-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.

Keywords: Genome-wide association studies; escape variants; hepatitis B virus; human leukocyte antigen; major histocompatibility complex; vaccination.

Publication types

Preprint

Abstract

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