Heterologous humoral immunity to human and zoonotic coronaviruses: Aiming for the achilles heel.
Heterologous humoral immunity to human and zoonotic coronaviruses: Aiming for the achilles heel.
复制标题
DOI：
10.1016/j.smim.2021.101507
复制
发表时间：
2021-06
影响因子：
7.8
通讯作者：
Kassiotis G
中科院分区：
文献类型：
--
作者：
Ng KW;Faulkner N;Wrobel AG;Gamblin SJ;Kassiotis G
冠状病毒是进化上成功的RNA病毒，常见于多种鸟类、两栖动物和哺乳动物宿主。尽管它们普遍存在并具有潜在影响，但对冠状病毒的宿主免疫力的了解仍然不完整，部分原因是地方性人类冠状病毒（HCoV）缺乏明显的致病性，而HCoV通常会导致普通感冒。然而，随着过去二十年中三种新型冠状病毒的人畜共患引入，导致人类严重急性呼吸道综合征，以及由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）大流行，更深入了解的需求变得迫切。这种新的兴趣不仅引发了四种HCoV中两种的发现，而且还发现了与共享或相关冠状病毒抗原的大量细胞和体液交叉反应性。在这里，我们回顾了交叉反应性B细胞记忆引起的HCoV及其对SARS-CoV-2感染的令人困惑的可变结果的潜在影响的证据。现有数据表明，交叉反应性B细胞和抗体主要靶向HCoV和SARS-CoV-2刺突糖蛋白S2亚基中的高度保守区域。罕见的单克隆抗体与保守的S2表位和有效的病毒中和活性反应已被克隆，强调交叉反应的潜在功能相关性。我们讨论了B细胞和抗体的交叉反应性在更广泛的背景下异源体液免疫冠状病毒，以及保护性免疫记忆对同源再感染的限制。鉴于交叉反应的双向性，目前针对SARS-CoV-2的前所未有的疫苗接种活动预计将影响HCoV，以及未来试图跨越物种屏障的人畜共患冠状病毒。然而，新出现的SARS-CoV-2变异体对疫苗诱导的抗体的中和具有抗性，这突出了对靶向刺突的更受约束、更不易变的部分的需要。这种交叉反应区域的划分，可以训练体液免疫来攻击，可能是永久改变我们与当前和未来冠状病毒相互作用平衡的关键。
Coronaviruses are evolutionarily successful RNA viruses, common to multiple avian, amphibian and mammalian hosts. Despite their ubiquity and potential impact, knowledge of host immunity to coronaviruses remains incomplete, partly owing to the lack of overt pathogenicity of endemic human coronaviruses (HCoVs), which typically cause common colds. However, the need for deeper understanding became pressing with the zoonotic introduction of three novel coronaviruses in the past two decades, causing severe acute respiratory syndromes in humans, and the unfolding pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This renewed interest not only triggered the discovery of two of the four HCoVs, but also uncovered substantial cellular and humoral cross-reactivity with shared or related coronaviral antigens. Here, we review the evidence for cross-reactive B cell memory elicited by HCoVs and its potential impact on the puzzlingly variable outcome of SARS-CoV-2 infection. The available data indicate targeting of highly conserved regions primarily in the S2 subunits of the spike glycoproteins of HCoVs and SARS-CoV-2 by cross-reactive B cells and antibodies. Rare monoclonal antibodies reactive with conserved S2 epitopes and with potent virus neutralising activity have been cloned, underscoring the potential functional relevance of cross-reactivity. We discuss B cell and antibody cross-reactivity in the broader context of heterologous humoral immunity to coronaviruses, as well as the limits of protective immune memory against homologous re-infection. Given the bidirectional nature of cross-reactivity, the unprecedented current vaccination campaign against SARS-CoV-2 is expected to impact HCoVs, as well as future zoonotic coronaviruses attempting to cross the species barrier. However, emerging SARS-CoV-2 variants with resistance to neutralisation by vaccine-induced antibodies highlight a need for targeting more constrained, less mutable parts of the spike. The delineation of such cross-reactive areas, which humoral immunity can be trained to attack, may offer the key to permanently shifting the balance of our interaction with current and future coronaviruses in our favour.
登录
查看更多内容
DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
15.9
作者：
Dangi, Tanushree;Palacio, Nicole;Penaloza-MacMaster, Pablo
通讯作者：
Penaloza-MacMaster, Pablo
影响因子：
56.9
作者：
Cai, Yongfei;Zhang, Jun;Chen, Bing
通讯作者：
Chen, Bing
DOI：
10.1128/cdli.12.11.1317-1321.2005
发表时间：
2005-11-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Chan, KH;Cheng, VCC;Peiris, JSM
通讯作者：
Peiris, JSM
影响因子：
6.7
作者：
Eguia RT;Crawford KHD;Stevens-Ayers T;Kelnhofer-Millevolte L;Greninger AL;Englund JA;Boeckh MJ;Bloom JD
通讯作者：
Bloom JD