Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455.
Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
J Immunol. 2021 Mar 1;206(5):931-935. doi: 10.4049/jimmunol.2001400. Epub 2021 Jan 13.
The magnitude of SARS-CoV-2-specific T cell responses correlates inversely with human disease severity, suggesting T cell involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited T cell immunity may bolster durable protection or cross-reactivity with viral variants. To better enable mechanistic and vaccination studies in mice, we identified a dominant CD8 T cell SARS-CoV-2 nucleoprotein epitope. Infection of human ACE2 transgenic mice with SARS-CoV-2 elicited robust responses to H2-D/N, and 40% of HLA-A*02 COVID-19 PBMC samples isolated from hospitalized patients responded to this peptide in culture. In mice, i.m. prime-boost nucleoprotein vaccination with heterologous vectors favored systemic CD8 T cell responses, whereas intranasal boosting favored respiratory immunity. In contrast, a single i.v. immunization with recombinant adenovirus established robust CD8 T cell memory both systemically and in the respiratory mucosa.
SARS-CoV-2 特异性 T 细胞反应的程度与人类疾病的严重程度呈负相关，这表明 T 细胞参与了原发性控制。虽然许多 COVID-19 疫苗专注于建立针对病毒刺突蛋白的体液免疫，但疫苗诱导的 T 细胞免疫可能增强持久的保护或与病毒变体的交叉反应性。为了在小鼠中更好地进行机制和疫苗接种研究，我们鉴定了一个主导的 CD8 T 细胞 SARS-CoV-2 核蛋白表位。用 SARS-CoV-2 感染人 ACE2 转基因小鼠引起了对 H2-D/N 的强烈反应，并且从住院患者中分离的 40%的 HLA-A*02 COVID-19 PBMC 样本在培养中对该肽产生反应。在小鼠中，用异源载体进行肌内初免-加强核蛋白疫苗接种有利于全身 CD8 T 细胞反应，而鼻内加强有利于呼吸道免疫。相比之下，单次静脉内免疫用重组腺病毒建立了强大的 CD8 T 细胞记忆，无论是在全身还是在呼吸道黏膜中。
