Lisette Alcantara Sanchez, Eloy Alvarez Guerra, Dongmei Li, Samantha M King, Shannon P Hilchey, Qian Zhou, Stephen Dewhurst, Kevin Fiscella, Martin S Zand
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引用次数: 0
Abstract
Background: Vaccination against SARS-CoV-2 has been pivotal in controlling the COVID-19 pandemic. However, understanding vaccine-induced immunity in immunocompromised individuals remains critical, particularly how prior exposure to other coronaviruses modulates immune responses. The influence of previous infections with endemic human coronaviruses (HCoVs), such as OC43, on SARS-CoV-2 immunity is not fully understood. This study evaluates antibody responses to COVID-19 vaccination in hemodialysis patients (HD), transplant recipients (TR), and healthy controls (CO), accounting for prior SARS-CoV-2 infection and baseline human coronavirus (HCoV) reactivity. Methods: We obtained longitudinal antibody measurements from 70 subjects (CO: n = 33; HD: n = 13; TR: n = 24) and assessed antibody kinetics across multiple post-vaccination time points using multivariate linear mixed modeling (MLMM). Results: Limited but measurable cross-reactivity was observed between SARS-CoV-2 and endemic HCoVs, particularly the β-coronavirus OC43. Pre-existing immunity in healthy individuals modestly enhanced vaccine-induced anti-spike (S) IgG responses, supported by post-vaccination increases in SARS-CoV-2 IgG. Prior SARS-CoV-2 infection significantly influenced anti-S and nucleocapsid (N) IgG responses but had limited impact on endemic HCoVs responses. Vaccine type and immune status significantly affected antibody kinetics. mRNA vaccination (BNT162b2) elicited stronger and more durable SARS-CoV-2 anti-S IgG responses than the inactivated CoronaVac vaccine, especially in immunocompetent individuals. Immunocompromised groups showed delayed or attenuated responses, with modest anti-S IgG cross-reactive boosting. Elevated anti-N IgG in CoronaVac recipients raised questions about its origin-infection or vaccine effects. MLMM identified key immunological and clinical predictors of antibody responses, emphasizing the critical role of host immune history. Conclusions: These findings highlight a constrained but meaningful role for HCoV cross-reactivity in SARS-CoV-2 immunity and vaccine responsiveness, underscore the need for infection markers unaffected by vaccination, and support development of broadly protective pan-coronavirus vaccines and tailored strategies for at-risk populations.
背景:针对SARS-CoV-2的疫苗接种是控制COVID-19大流行的关键。然而,了解免疫功能低下个体的疫苗诱导免疫仍然至关重要,特别是先前暴露于其他冠状病毒如何调节免疫反应。以前感染地方性人类冠状病毒(hcov),如OC43,对SARS-CoV-2免疫的影响尚不完全清楚。本研究评估了血液透析患者(HD)、移植受者(TR)和健康对照(CO)对COVID-19疫苗接种的抗体反应,考虑了先前的SARS-CoV-2感染和基线人冠状病毒(HCoV)反应。方法:我们获得了70名受试者(CO: n = 33; HD: n = 13; TR: n = 24)的纵向抗体测量数据,并使用多元线性混合模型(MLMM)评估了接种后多个时间点的抗体动力学。结果:在SARS-CoV-2和地方性hcov之间观察到有限但可测量的交叉反应性,特别是β-冠状病毒OC43。健康个体的预先免疫适度增强了疫苗诱导的抗刺突(S) IgG应答,这得到了接种后SARS-CoV-2 IgG升高的支持。先前的SARS-CoV-2感染显著影响抗s和核衣壳(N) IgG反应,但对地方性hcov反应影响有限。疫苗类型和免疫状态显著影响抗体动力学。与灭活的冠状病毒疫苗相比,mRNA疫苗(BNT162b2)引发了更强、更持久的SARS-CoV-2抗s IgG应答,尤其是在免疫能力强的个体中。免疫功能低下组反应延迟或减弱,抗s IgG交叉反应增强。冠状病毒受体中抗- n IgG升高引发了对其来源感染或疫苗效果的质疑。MLMM确定了抗体反应的关键免疫学和临床预测因子,强调了宿主免疫史的关键作用。结论:这些发现强调了HCoV交叉反应性在SARS-CoV-2免疫和疫苗反应性中的作用有限但有意义,强调了对不受疫苗接种影响的感染标志物的需求,并支持开发具有广泛保护性的泛冠状病毒疫苗和针对高危人群的量身定制策略。
VaccinesPharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
8.90
自引率
16.70%
发文量
1853
审稿时长
18.06 days
期刊介绍:
Vaccines (ISSN 2076-393X) is an international, peer-reviewed open access journal focused on laboratory and clinical vaccine research, utilization and immunization. Vaccines publishes high quality reviews, regular research papers, communications and case reports.