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

tetano

Editor, Senior Moderator
Vaccine


. 2025 Jun 16:61:127379.
doi: 10.1016/j.vaccine.2025.127379. Online ahead of print. Genetic markers of enhanced functional antibody responses to COVID-19 vaccination

Ruth A Purcell[SUP] 1 [/SUP], L Carissa Aurelia[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Katherine A Bond[SUP] 2 [/SUP], Deborah A Williamson[SUP] 3 [/SUP], Janine M Trevillyan[SUP] 4 [/SUP], Jason A Trubiano[SUP] 5 [/SUP], Bruce D Wines[SUP] 6 [/SUP], P Mark Hogarth[SUP] 7 [/SUP], Jennifer A Juno[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Kanta Subbarao[SUP] 8 [/SUP], Katherine Kedzierska[SUP] 1 [/SUP], Stephen J Kent[SUP] 9 [/SUP], Siddhartha Mahanty[SUP] 10 [/SUP], Kevin John Selva[SUP] 1 [/SUP], Amy W Chung[SUP] 11 [/SUP]



Affiliations
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[SUP]+/+[/SUP] compared to G1m-1,3[SUP]+/+[/SUP] 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[SUP]+/+[/SUP] vaccinees, facilitating increased RBD-specific FcγR2a-R131 and FcγR2b binding.
Conclusion: Primary COVID-19 vaccination induced increased S2-specific IgG in G1m1,17[SUP]+/+[/SUP] vaccinees, facilitating enhanced anti-viral FcγR engagement and suggesting immunogenetics may be a valuble consideration for next-generation vaccine design.

Keywords: Fc functions; FcγR polymorphism; IgG Allotype; Immunogenetics; SARS-CoV-2; Vaccine.

 
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