The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies has indicated the importance of T cell responses against this virus. In this study, we highlight the SARS-CoV-2 epitopes that induce potent T cell responses and discuss whether T cell responses alone are adequate to confer protection against SARS-CoV-2 and describe the administration of 20 peptides with an RNA adjuvant in mice. The peptides have been synthesized based on SARS-CoV-2 spike and nucleocapsid protein sequences. Our study demonstrates that immunization with these peptides significantly increases the proportion of effector memory T cell population and interferon-γ (IFN-γ)-, interleukin-4 (IL-4)-, tumor necrosis factor-α (TNF-α)-, and granzyme B-producing T cells. Of these 20 peptides, four induce the generation of IFN-γ-producing T cells, elicit CD8⁺ T cell (CTL) responses in a dose-dependent manner, and induce cytotoxic T lymphocytes that eliminate peptide-pulsed target cells in vivo. Although it is not statistically significant, these peptide vaccines reduce viral titers in infected hamsters and alleviate pulmonary pathology in SARS-CoV-2-infected human ACE2 transgenic mice. These findings may aid the design of effective SARS-CoV-2 peptide vaccines, while providing insights into the role of T cells in SARS-CoV-2 infection.

逃避疫苗诱导的中和抗体的严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 变体的出现表明了 T 细胞对这种病毒的反应的重要性。在这项研究中，我们重点介绍了诱导有效 T 细胞反应的 SARS-CoV-2 表位，并讨论了单独的 T 细胞反应是否足以提供针对 SARS-CoV-2 的保护，并描述了在小鼠中使用 20 种肽和 RNA 佐剂. 这些肽是基于 SARS-CoV-2 刺突和核衣壳蛋白序列合成的。我们的研究表明，用这些肽免疫显着增加了效应记忆 T 细胞群和干扰素-γ (IFN-γ)-、白细胞介素-4 (IL-4)-、肿瘤坏死因子-α (TNF-α)- 的比例和产生颗粒酶 B 的 T 细胞。在这 20 种肽中，⁺ T 细胞 (CTL) 反应以剂量依赖性方式，并诱导细胞毒性 T 淋巴细胞消除肽脉冲靶细胞体内. 尽管没有统计学意义，但这些肽疫苗降低了受感染仓鼠的病毒滴度，并减轻了 SARS-CoV-2 感染的人类 ACE2 转基因小鼠的肺部病理。这些发现可能有助于设计有效的 SARS-CoV-2 肽疫苗，同时提供对 T 细胞在 SARS-CoV-2 感染中的作用的见解。