Harbour Jake C, Lyski Zoe L, Schell John B, Thomas Archana, Messer William B, Slifka Mark K, Nolz Jeffrey C
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR.
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR.
J Immunol. 2021 Jun 1;206(11):2596-2604. doi: 10.4049/jimmunol.2100054. Epub 2021 May 10.
The COVID-19 pandemic is a global health emergency, and the development of a successful vaccine will ultimately be required to prevent the continued spread and seasonal recurrence of this disease within the human population. However, very little is known about either the quality of the adaptive immune response or the viral Ag targets that will be necessary to prevent the spread of the infection. In this study, we generated recombinant Vaccinia virus expressing the full-length spike protein from SARS-CoV-2 (VacV-S) to evaluate the cellular and humoral immune response mounted against this viral Ag in mice. Both CD8 and CD4 T cells specific to the SARS-CoV-2 spike protein underwent robust expansion, contraction, and persisted for at least 40 d following a single immunization with VacV-S. Vaccination also caused the rapid emergence of spike-specific IgG-neutralizing Abs. Interestingly, both the cellular and humoral immune responses strongly targeted the S1 domain of spike following VacV-S immunization. Notably, immunization with VacV-expressing spike conjugated to the MHC class II invariant chain, a strategy previously reported by us and others to enhance the immunogenicity of antigenic peptides, did not promote stronger spike-specific T cell or Ab responses in vivo. Overall, these findings demonstrate that an immunization approach using VacV or attenuated versions of VacV expressing the native, full-length SARS-CoV-2 spike protein could be used for further vaccine development to prevent the spread of COVID-19.
新型冠状病毒肺炎（COVID-19）大流行是一场全球卫生突发事件，最终需要研发出成功的疫苗来预防该疾病在人群中的持续传播和季节性复发。然而，对于适应性免疫反应的质量或预防感染传播所需的病毒抗原靶点，我们知之甚少。在本研究中，我们构建了表达严重急性呼吸综合征冠状病毒2（SARS-CoV-2）全长刺突蛋白的重组痘苗病毒（VacV-S），以评估小鼠针对该病毒抗原产生的细胞免疫和体液免疫反应。用VacV-S单次免疫后，针对SARS-CoV-2刺突蛋白的CD8和CD4 T细胞均经历了强劲的扩增、收缩，并持续至少40天。接种疫苗还导致了刺突特异性IgG中和抗体的快速出现。有趣的是，VacV-S免疫后，细胞免疫和体液免疫反应均强烈靶向刺突的S1结构域。值得注意的是，用与MHC II类恒定链偶联的刺突蛋白表达的痘苗病毒免疫，这是我们和其他人先前报道的一种增强抗原肽免疫原性的策略，在体内并未促进更强的刺突特异性T细胞或抗体反应。总体而言，这些发现表明，使用VacV或表达天然全长SARS-CoV-2刺突蛋白的减毒痘苗病毒的免疫方法可用于进一步的疫苗研发，以预防COVID-19的传播。
