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Publications

Journal Article Ppublish

PubMed: 40527060 DOI: 10.1016/j.vaccine.2025.127379

Genetic markers of enhanced functional antibody responses to COVID-19 vaccination.

Vaccine 61:127379

Authors: Ruth A Purcell, L Carissa Aurelia, Lilith F Allen, Katherine A Bond, Deborah A Williamson, Janine M Trevillyan, Jason A Trubiano, Bruce D Wines, P Mark Hogarth, Jennifer A Juno, Adam K Wheatley, Thi H O Nguyen, Kanta Subbarao, Katherine Kedzierska, Stephen J Kent, Siddhartha Mahanty, Kevin John Selva, Amy W Chung

Affiliations

  • Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Victorian Infectious Diseases Reference Laboratory (VIDRL), The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; School of Medicine, University of St Andrews, Fife, KY16 9TF, Scotland.
  • Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, VIC 3084, Australia.
  • Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, VIC 3084, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia; Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
  • Immune Therapies Group, Burnet Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
  • Immune Therapies Group, Burnet Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
  • Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.

Abstract

INTRODUCTION

Substantial population-level variation in vaccine-specific antibody responses has been observed following global coronavirus disease 2019 (COVID-19) vaccination efforts. Beyond the influence of clinical and demographic features, immunogenetic variation is suggested to underlie divergent serological responses following COVID-19 vaccination of distinct populations.

METHODS

Immunoglobulin G1 (IgG1) allotypic markers (G1m) for 121 COVID-19 vaccinated healthy adults were genotyped via Sanger sequencing. Vaccine-specific IgG and Fc gamma receptor (FcγR) engagement were characterised via bead-based multiplex array.

RESULTS

Following two COVID-19 vaccine doses, G1m1,17 +/+ compared to G1m-1,3 +/+ vaccinees had increased IgG and FcγR engagement specific for the antigenically conserved SARS-CoV-2 Spike 2 (S2) domain. IgG targeting antigenically novel SARS-CoV-2 receptor binding domain (RBD) trended higher in G1m1,17 +/+ vaccinees, facilitating increased RBD-specific FcγR2a-R131 and FcγR2b binding.

CONCLUSION

Primary COVID-19 vaccination induced increased S2-specific IgG in G1m1,17 +/+ vaccinees, facilitating enhanced anti-viral FcγR engagement and suggesting immunogenetics may be a valuble consideration for next-generation vaccine design.

MeSH

Antibody Formation, Immunogenetics, Vaccines, Vaccination, Covid-19, Genetic Markers

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