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奥密克戎变异株感染增强了三剂科兴疫苗接种者的全身性和黏膜免疫的幅度和持久性。

SARS-CoV-2 Omicron infection augments the magnitude and durability of systemic and mucosal immunity in triple-dose CoronaVac recipients.

机构信息

Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.

Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.

出版信息

mBio. 2024 Apr 10;15(4):e0240723. doi: 10.1128/mbio.02407-23. Epub 2024 Mar 8.

DOI:10.1128/mbio.02407-23
PMID:38456703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11005357/
Abstract

UNLABELLED

The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4 and CD8 T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4 T cells, and memory CD8 T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection.

IMPORTANCE

There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection.

CLINICAL TRIAL

This study is registered with ClinicalTrials.gov as NCT05680896.

摘要

未加说明

灭活全病毒疫苗科兴疫苗是目前世界范围内使用最广泛的 2019 冠状病毒病(COVID-19)疫苗之一。关于该疫苗诱导的免疫反应持久性以及对奥密克戎感染免疫印迹的影响,目前数据较少。在这项前瞻性队列研究中,招募了 41 名接受三剂科兴疫苗接种者和 14 名未接种者。我们全面分析了两组的适应性免疫参数,包括刺突特异性免疫球蛋白(Ig)G 和 IgA 滴度、中和活性、B 细胞、循环滤泡辅助 T(cTfh)细胞、CD4 和 CD8 T 细胞及其记忆亚群,这些参数在第三剂加强针接种后 12 个月以及感染奥密克戎 BA.5 后 4 周和 20 周进行检测。在第三剂科兴疫苗接种后 12 个月,大多数接种者仍可检测到刺突特异性抗体和细胞反应。与未接种者相比,奥密克戎 BA.5 感染显著增强了血清中和活性、Fc 介导的吞噬作用、鼻内刺突特异性 IgA 反应、记忆 B 细胞、活化的 cTfh 细胞、记忆 CD4 T 细胞和记忆 CD8 T 细胞的数量、交叉反应性和持久性,无论是针对原始株还是奥密克戎亚变体。值得注意的是,突破性感染后 BA.5 特异性免疫的增加与原始株相当或高于原始株,这表明没有免疫印迹的证据。免疫图谱分析表明,与未接种者相比,接种者在异源感染时,多种免疫成分的同步性更好。我们的数据提供了关于灭活 COVID-19 疫苗在塑造针对奥密克戎感染的体液和细胞免疫方面的保护作用的详细信息。

重要性

目前关于科兴疫苗诱导的免疫反应持久性以及对奥密克戎突破感染免疫印迹的影响的数据较少。在这项前瞻性队列研究中,我们分析了奥密克戎 BA.5 感染前后针对严重急性呼吸综合征冠状病毒 2 的适应性反应。我们的数据提供了关于灭活 COVID-19 疫苗在塑造针对异源奥密克戎感染的体液和细胞免疫反应方面的保护作用的详细信息。

临床试验

本研究在 ClinicalTrials.gov 注册,注册号为 NCT05680896。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970a/11005357/dd694f039952/mbio.02407-23.f006.jpg
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