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既往免疫会限制黏膜抗体对 SARS-CoV-2 的识别，以及突破感染期间的 Fc 特征。

Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections.

机构信息

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.

Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.

出版信息

JCI Insight. 2023 Sep 22;8(18):e172470. doi: 10.1172/jci.insight.172470.

DOI:10.1172/jci.insight.172470
PMID:37737263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10561726/
Abstract

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19-recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19-recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19-uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2-specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2-specific antibody responses and has implications for long-term protection from COVID-19.

摘要

了解 SARS-CoV-2 感染和/或接种疫苗引起的黏膜抗体反应对于制定更长期免疫策略至关重要，特别是针对新出现的病毒变体。我们对仅接种过 COVID-19 疫苗的疫苗接种者（接种、未感染）、COVID-19 康复的疫苗接种者（康复、接种）以及突破性德尔塔或奥密克戎 BA.2 感染的个体（接种、感染）的连续配对黏膜和血浆抗体进行了分析。与 COVID-19 未感染的疫苗接种者相比，COVID-19 康复的疫苗接种者的唾液显示出改善的抗体中和活性、Fcγ 受体（FcγR）结合和 IgA 水平。此外，重复的 mRNA 疫苗接种可增强黏膜生物体液（唾液和眼泪）和血浆中 SARS-CoV-2 特异性 IgG2 和 IgG4 反应；然而，这些增加仅与血浆中的 FcγR 结合呈负相关。针对突破性 COVID-19 变体的 IgG 和 FcγR 结合反应，但不是 IgA 反应，被针对原始株的增加的预先存在的疫苗诱导的免疫所抑制和变窄。唾液抗体在突破性 COVID-19 感染后延迟启动，特别是奥密克戎 BA.2，但此后迅速上升。重要的是，突破感染后唾液抗体的 FcγR 结合增强。我们的数据强调了先前存在的免疫如何塑造 SARS-CoV-2 特异性黏膜抗体反应，并对 COVID-19 的长期保护具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/1e83c21bb833/jciinsight-8-172470-g113.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/4b85b6f24632/jciinsight-8-172470-g106.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/3253feb42b33/jciinsight-8-172470-g107.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/c38fee913f49/jciinsight-8-172470-g108.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/a30072c08d3c/jciinsight-8-172470-g109.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/a7b9cc6c5d6b/jciinsight-8-172470-g110.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/a0bab977ecf1/jciinsight-8-172470-g111.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/040ff0f269d2/jciinsight-8-172470-g112.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/1e83c21bb833/jciinsight-8-172470-g113.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/4b85b6f24632/jciinsight-8-172470-g106.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/3253feb42b33/jciinsight-8-172470-g107.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/c38fee913f49/jciinsight-8-172470-g108.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/a30072c08d3c/jciinsight-8-172470-g109.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/a7b9cc6c5d6b/jciinsight-8-172470-g110.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/a0bab977ecf1/jciinsight-8-172470-g111.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/040ff0f269d2/jciinsight-8-172470-g112.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2013/10561726/1e83c21bb833/jciinsight-8-172470-g113.jpg

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