The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

Publication

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


Authors:

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

Details:

Vaccine, Volume 61, 2025-08-13

Article Link: Click here

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.