A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8⁺ T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8⁺ T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.

要完全控制严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的流行，可能需要结合多种疫苗接种方法。在这里，我们发现表达膜锚定融合前稳定刺突（MVA/S）但不分泌S1的改良痘苗安卡拉（MVA）载体在小鼠中诱导针对SARS-CoV-2的强烈中和抗体反应。在猕猴中，MVA/S 疫苗接种诱导产生强中和抗体和 CD8 ⁺T 细胞反应，并在鼻内和气管内攻击后的第 2 天就提供了针对 SARS-CoV-2 感染和病毒在肺部复制的保护。感染后第 4 天对肺细胞的单细胞 RNA 测序分析表明，MVA/S 疫苗接种还可以保护猕猴免受感染引起的炎症和 B 细胞异常的影响，并降低干扰素刺激基因的诱导。这些结果表明，MVA/S 疫苗接种可诱导血液和肺部中的中和抗体和 CD8 ⁺ T 细胞，是 SARS-CoV-2 的潜在候选疫苗。