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.