Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-11-05 DOI:10.1016/j.celrep.2024.114922
Jordan J Clark, Irene Hoxie, Daniel C Adelsberg, Iden A Sapse, Robert Andreata-Santos, Jeremy S Yong, Fatima Amanat, Johnstone Tcheou, Ariel Raskin, Gagandeep Singh, Irene González-Domínguez, Julia E Edgar, Stylianos Bournazos, Weina Sun, Juan Manuel Carreño, Viviana Simon, Ali H Ellebedy, Goran Bajic, Florian Krammer
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Abstract

Neutralizing antibodies correlate with protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection against disease progression. Non-neutralizing antibodies cannot directly protect against infection but may recruit effector cells and thus contribute to the clearance of infected cells. Additionally, they often bind conserved epitopes across multiple variants. Here, we characterize 42 human monoclonal antibodies (mAbs) from coronavirus disease 2019 (COVID-19)-vaccinated individuals. Most of these antibodies exhibit no neutralizing activity in vitro, but several non-neutralizing antibodies provide protection against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs shows a clear dependence on Fc-mediated effector functions. We have determined the structures of three non-neutralizing antibodies, with two targeting the receptor-binding domain and one that binds the subdomain 1 region. Our data confirm the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.

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接种SARS-CoV-2 mRNA引起的人类非中性交叉反应性尖峰抗体的保护作用和分子机制。
中和抗体与预防严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)有关。然而,最近的研究表明,在没有强大中和活性的情况下,结合抗体滴度也与防止疾病恶化有关。非中和性抗体不能直接抵御感染,但可以招募效应细胞,从而有助于清除受感染的细胞。此外,它们通常与多个变体的保守表位结合。在这里,我们对接种过冠状病毒病 2019(COVID-19)疫苗的人体内的 42 种人类单克隆抗体(mAbs)进行了鉴定。这些抗体中的大多数在体外没有表现出中和活性,但有几种非中和抗体在不同的动物模型中对 SARS-CoV-2 的致死性挑战有保护作用。这些 mAbs 中的一个子集明显依赖于 Fc 介导的效应器功能。我们测定了三种非中性抗体的结构,其中两种以受体结合域为靶标,一种结合亚域 1 区域。我们的数据证实了在人体中观察到的实际情况,即针对 SARS-CoV-2 的非中和抗体可以起到保护作用。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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