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

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

doi:10.1016/j.vaccine.2025.127379

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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. 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. 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. 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. [Abstract copyright: Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.]

Original language	English
Article number	127379
Journal	Vaccine
Volume	61
Early online date	16 Jun 2025
DOIs	https://doi.org/10.1016/j.vaccine.2025.127379
Publication status	Published - 13 Aug 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Vaccine
IgG Allotype
SARS-CoV-2
Fc functions
FcγR polymorphism
Immunogenetics

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Copyright © 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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Purcell, R. A., Aurelia, L. C., Allen, L. F., Bond, K. A., Williamson, D. A., Trevillyan, J. M., Trubiano, J. A., Wines, B. D., Hogarth, P. M., Juno, J. A., Wheatley, A. K., Nguyen, T. H. O., Subbarao, K., Kedzierska, K., Kent, S. J., Mahanty, S., Selva, K. J., & Chung, A. W. (2025). Genetic markers of enhanced functional antibody responses to COVID-19 vaccination. Vaccine, 61, Article 127379. https://doi.org/10.1016/j.vaccine.2025.127379

@article{637f7f449f804c68b8938e6471951cb2,

title = "Genetic markers of enhanced functional antibody responses to COVID-19 vaccination",

abstract = "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. 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. 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. 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. [Abstract copyright: Copyright {\textcopyright} 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.]",

keywords = "Vaccine, IgG Allotype, SARS-CoV-2, Fc functions, FcγR polymorphism, Immunogenetics",

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

note = "Funding: This study was supported by a Medical Research Future Fund (MRFF) GNT \#2016062 to JAT, JAJ, AKW, THON, KK, SJK, and AWC, and a National Health and Medical Research Council (NHMRC) Investigator grant \#2008092 to AWC. JAJ, AKW, THON, KS, KK, and SJK are also supported by NHMRC Investigator grants. JAJ is also supported by the Charles and Sylvia Viertel Charitable Foundation. The DISCOVER-HCP study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Centers of Excellence for Influenza Research and Response (CEIRR) grant \#HHSN272201400005C to the University of Rochester and a subcontract to KS. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.",

year = "2025",

month = aug,

day = "13",

doi = "10.1016/j.vaccine.2025.127379",

language = "English",

volume = "61",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

}

Purcell, RA, Aurelia, LC, Allen, LF, Bond, KA, Williamson, DA, Trevillyan, JM, Trubiano, JA, Wines, BD, Hogarth, PM, Juno, JA, Wheatley, AK, Nguyen, THO, Subbarao, K, Kedzierska, K, Kent, SJ, Mahanty, S, Selva, KJ & Chung, AW 2025, 'Genetic markers of enhanced functional antibody responses to COVID-19 vaccination', Vaccine, vol. 61, 127379. https://doi.org/10.1016/j.vaccine.2025.127379

TY - JOUR

T1 - Genetic markers of enhanced functional antibody responses to COVID-19 vaccination

AU - Purcell, Ruth A

AU - Aurelia, L Carissa

AU - Allen, Lilith F

AU - Bond, Katherine A

AU - Williamson, Deborah A

AU - Trevillyan, Janine M

AU - Trubiano, Jason A

AU - Wines, Bruce D

AU - Hogarth, P Mark

AU - Juno, Jennifer A

AU - Wheatley, Adam K

AU - Nguyen, Thi H O

AU - Subbarao, Kanta

AU - Kedzierska, Katherine

AU - Kent, Stephen J

AU - Mahanty, Siddhartha

AU - Selva, Kevin John

AU - Chung, Amy W

N1 - Funding: This study was supported by a Medical Research Future Fund (MRFF) GNT #2016062 to JAT, JAJ, AKW, THON, KK, SJK, and AWC, and a National Health and Medical Research Council (NHMRC) Investigator grant #2008092 to AWC. JAJ, AKW, THON, KS, KK, and SJK are also supported by NHMRC Investigator grants. JAJ is also supported by the Charles and Sylvia Viertel Charitable Foundation. The DISCOVER-HCP study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Centers of Excellence for Influenza Research and Response (CEIRR) grant #HHSN272201400005C to the University of Rochester and a subcontract to KS. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.

PY - 2025/8/13

Y1 - 2025/8/13

N2 - 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. 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. 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. 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. [Abstract copyright: Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.]

AB - 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. 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. 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. 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. [Abstract copyright: Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.]

KW - Vaccine

KW - IgG Allotype

KW - SARS-CoV-2

KW - Fc functions

KW - FcγR polymorphism

KW - Immunogenetics

U2 - 10.1016/j.vaccine.2025.127379

DO - 10.1016/j.vaccine.2025.127379

M3 - Article

C2 - 40527060

SN - 0264-410X

VL - 61

JO - Vaccine

JF - Vaccine

M1 - 127379

ER -

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

Abstract

UN SDGs

Keywords

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