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^*

^*Corresponding author for this work

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

1 Citation (Scopus)

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.

Original language	English
Article number	127379
Journal	Vaccine
Volume	61
DOIs	https://doi.org/10.1016/j.vaccine.2025.127379
Publication status	Published - 13 Aug 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 The Authors

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

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10.1016/j.vaccine.2025.127379

Cite this

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{fc7d95b615bd4d698886519c6f5d39ef,

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

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.",

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

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 = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = aug,

day = "13",

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

language = "English",

volume = "61",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier Ltd.",

}

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.

PY - 2025/8/13

Y1 - 2025/8/13

N2 - 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.

AB - 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.

KW - Fc functions

KW - FcγR polymorphism

KW - IgG Allotype

KW - Immunogenetics

KW - SARS-CoV-2

KW - Vaccine

UR - https://www.scopus.com/pages/publications/105008105390

U2 - 10.1016/j.vaccine.2025.127379

DO - 10.1016/j.vaccine.2025.127379

M3 - Article

AN - SCOPUS:105008105390

SN - 0264-410X

VL - 61

JO - Vaccine

JF - Vaccine

M1 - 127379

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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