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恒河猴中 SARS-CoV-2 保护作用的相关因素。

Correlates of protection against SARS-CoV-2 in rhesus macaques.

机构信息

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.

出版信息

Nature. 2021 Feb;590(7847):630-634. doi: 10.1038/s41586-020-03041-6. Epub 2020 Dec 4.

DOI:10.1038/s41586-020-03041-6
PMID:33276369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7906955/
Abstract

Recent studies have reported the protective efficacy of both natural and vaccine-induced immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques (Macaca mulatta) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8 T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents.

摘要

最近的研究报告称，自然免疫和疫苗诱导免疫对恒河猴感染严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）都具有保护作用。然而，体液免疫和细胞免疫对于预防 SARS-CoV-2 感染的重要性仍有待确定。在这里，我们表明，从恢复期恒河猴（Macaca mulatta）中纯化的 IgG 的过继转移以剂量依赖的方式保护了幼稚受体猴免受 SARS-CoV-2 的攻击。在恢复期猕猴中耗尽 CD8 T 细胞部分消除了自然免疫对 SARS-CoV-2 再挑战的保护作用，这表明细胞免疫在抗体滴度下降或亚保护的情况下发挥作用。这些数据表明，相对较低的抗体滴度足以在恒河猴中预防 SARS-CoV-2，并且如果抗体反应不理想，细胞免疫反应可能有助于保护。我们还表明，在猕猴中治疗 SARS-CoV-2 感染需要更高的抗体滴度。这些发现对 SARS-CoV-2 疫苗和免疫治疗药物的开发具有重要意义。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/584e/7906955/dd2a98729703/nihms-1649751-f0013.jpg

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