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

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-06-16 DOI:10.1016/j.vaccine.2025.127379

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

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引用次数: 0

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.

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COVID-19疫苗接种增强功能性抗体反应的遗传标记

在全球2019冠状病毒病（COVID-19）疫苗接种工作之后，观察到疫苗特异性抗体反应在人群水平上存在实质性差异。除了临床和人口统计学特征的影响外，免疫遗传变异被认为是不同人群接种COVID-19疫苗后不同血清学反应的基础。方法采用Sanger测序法对121例健康成人COVID-19疫苗接种者的免疫球蛋白G1 （IgG1）异型标记物（G1m）进行基因分型。疫苗特异性IgG和Fcγ受体（Fcγ r）结合通过基于头部的多重阵列进行表征。结果接种两剂COVID-19疫苗后，与g1m -1,3+/+疫苗相比，G1m1、17+/+疫苗增加了特异性抗原保守的SARS-CoV-2 Spike 2 （S2）结构域的IgG和FcγR结合。在G1m1、17+/+疫苗中，IgG靶向抗原新颖的SARS-CoV-2受体结合域（RBD）呈升高趋势，促进了RBD特异性fc - γ - r2a - r131和fc - γ - r2b结合的增加。结论首次接种COVID-19疫苗可诱导G1m1、17+/+疫苗接种者的s2特异性IgG升高，促进了抗病毒fc - γ - r的结合，提示免疫遗传学可能是下一代疫苗设计的重要考虑因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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