Discrete SARS-CoV-2 antibody titers track with functional humoral stability.
Discrete SARS-CoV-2 antibody titers track with functional humoral stability.
复制标题
离散的 SARS-CoV-2 抗体滴度与功能性体液稳定性保持一致。
DOI：
10.1038/s41467-021-21336-8
复制
发表时间：
2021-02-15
影响因子：
16.6
通讯作者：
Alter G
中科院分区：
文献类型：
--
作者：
Bartsch YC;Fischinger S;Siddiqui SM;Chen Z;Yu J;Gebre M;Atyeo C;Gorman MJ;Zhu AL;Kang J;Burke JS;Slein M;Gluck MJ;Beger S;Hu Y;Rhee J;Petersen E;Mormann B;Aubin MS;Hasdianda MA;Jambaulikar G;Boyer EW;Sabeti PC;Barouch DH;Julg BD;Musk ER;Menon AS;Lauffenburger DA;Nilles EJ;Alter G
抗体可以作为感染的生物标志物，但如果持续存在，可以提供长期免疫力。然而，对于大多数临床批准的疫苗来说，结合抗体效价只是作为保护的替代。相反，疫苗诱导的抗体中和或调节Fc-效应器功能的能力与保护机制有关。虽然有证据表明SARS-CoV-2感染者的抗体反应持续存在，但再次感染的病例已经开始出现，这让人质疑体液免疫对这种高度传染性病原体的保护性质。通过一项以社区为基础的监测研究，我们的目标是确定SARS-CoV-2效价和功能性抗体活性之间的关系。在这里，我们报告了120个已鉴定的血清转换者中抗体滴度的显著异质性，但衰变有限，其中大多数人都有无症状感染。值得注意的是，只有在引起RBD特异性抗体效价高于阈值的受试者中，才能观察到中和、Fc功能和SARS-CoV-2特异性T细胞反应。这些发现指出了观察到的抗体效价和功能之间的开关关系，在这种关系中，需要一个明显的活动阈值-由抗体水平定义-才能引发强有力的体液和细胞反应。这种反应活动水平可能对持久保护至关重要，这可能解释了为什么SARS-CoV-2和其他常见冠状病毒会再次感染。针对SARS-CoV-2的抗体保护程度尚不清楚。在这里，作者使用120名血清转换个体的队列，纵向表征了中和、Fc功能和SARS-CoV-2特异性T细胞反应，他们表明，只有在那些诱导受体结合域(RBD)特异性抗体效价高于一定阈值的受试者中，这些反应才显著，这表明T细胞反应的发展与抗RBD抗体的产生有关。
Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity—defined by the level of antibodies—is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses. The extent of antibody protection against SARS-CoV-2 remains unclear. Here, using a cohort of 120 seroconverted individuals, the authors longitudinally characterize neutralization, Fc-function, and SARS-CoV-2 specific T cell responses, which they show to be prominent only in those subjects that elicited receptor-binding domain (RBD)-specific antibody titers above a certain threshold, suggesting that development of T cell responses to be related to anti-RBD Ab production.
登录
查看更多内容
影响因子：
2.2
作者：
Karsten, Christina B.;Mehta, Nickita;Alter, Galit
通讯作者：
Alter, Galit
影响因子：
82.9
作者：
Long, Quan-Xin;Liu, Bai-Zhong;Huang, Ai-Long
通讯作者：
Huang, Ai-Long
影响因子：
11.8
作者：
Plotkin, Stanley A.
通讯作者：
Plotkin, Stanley A.
影响因子：
158.5
作者：
Keech, Cheryl;Albert, Gary;Glenn, Gregory M.
通讯作者：
Glenn, Gregory M.
影响因子：
2.2
作者：
Brown EP;Weiner JA;Lin S;Natarajan H;Normandin E;Barouch DH;Alter G;Sarzotti-Kelsoe M;Ackerman ME
通讯作者：
Ackerman ME