Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against SARS-CoV-2 infection. Recently, robust vaccine prevention of severe disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters for virologic control. However, direct data demonstrating a role of CD8 + T cells in vaccine protection has not yet been reported. In this study, we show that vaccine-elicited CD8 + T cells contribute substantially to virologic control following SARS-CoV-2 challenge in rhesus macaques. We vaccinated 30 macaques with a single immunization of the adenovirus vector-based vaccine Ad26.COV2.S or sham and then challenged them with 5x10 5 TCID 50 SARS-CoV-2 B.1.617.2 (Delta) by the intranasal and intratracheal routes. All vaccinated animals were infected by this high-dose challenge but showed rapid virologic control in nasal swabs and bronchoalveolar lavage by day 4 following challenge. However, administration of an anti-CD8α or anti-CD8β depleting monoclonal antibody in vaccinated animals prior to SARS-CoV-2 challenge resulted in higher levels of peak and day 4 virus in both the upper and lower respiratory tracts. These data demonstrate that CD8 + T cells contribute substantially to vaccine protection against SARS-CoV-2 replication in macaques.

中文翻译：

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CD8 T 细胞有助于疫苗对猕猴的 SARS-CoV-2 保护作用

刺突特异性中和抗体 (NAb) 通常被认为是疫苗保护免受 SARS-CoV-2 感染的关键相关因素。最近，已经报道了使用很大程度上逃避 NAb 反应的 SARS-CoV-2 变体对严重疾病进行强有力的疫苗预防，这表明其他免疫参数在病毒学控制中的作用。然而，直接数据表明 CD8 的作用+T细胞在疫苗保护中的作用尚未见报道。在这项研究中，我们表明疫苗诱导的 CD8+在恒河猴受到 SARS-CoV-2 攻击后，T 细胞对病毒学控制做出了重大贡献。我们用基于腺病毒载体的疫苗 Ad26.COV2.S 或假疫苗对 30 只猕猴进行单次免疫接种，然后用 5x105个TCID50SARS-CoV-2 B.1.617.2 (Delta) 通过鼻内和气管内途径。所有接种疫苗的动物都受到这种高剂量攻击的感染，但在攻击后第 4 天鼻拭子和支气管肺泡灌洗液中显示出快速的病毒学控制。然而，在 SARS-CoV-2 攻击之前对接种疫苗的动物施用抗 CD8α 或抗 CD8β 耗竭单克隆抗体导致上呼吸道和下呼吸道的峰值和第 4 天病毒水平更高。这些数据表明 CD8+T 细胞极大地促进了针对猕猴 SARS-CoV-2 复制的疫苗保护。