Tissue-resident memory CD8 T-cell responses elicited by a single injection of a multi-target COVID-19 vaccine

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which enters the body principally through the nasal and larynx mucosa and progress to the lungs through the respiratory tract. SARS-CoV-2 replicates efficiently in respiratory epithelial cells motivating the development of alternative and rapidly scalable vaccine inducing mucosal protective and long-lasting immunity. We have previously developed an immunologically optimized multi-neoepitopes-based peptide vaccine platform which has already demonstrated tolerance and efficacy in hundreds of lung cancer patients. Here, we present a multi-target CD8 T cell peptide COVID-19 vaccine design targeting several structural (S, M, N) and non-structural (NSPs) SARS-CoV-2 proteins with selected epitopes in conserved regions of the SARS-CoV-2 genome. We observed that a single subcutaneous injection of a serie of epitopes induces a robust immunogenicity in-vivo as measured by IFNγ ELIspot. Upon tetramer characterization we found that this serie of epitopes induces a strong proportion of virus-specific CD8 T cells expressing CD103, CD44, CXCR3 and CD49a, the specific phenotype of tissue-resident memory T lymphocytes (Trm). Finally, we observed broad cellular responses, as characterized by IFNγ production, upon restimulation with structural and non-structural protein-derived epitopes using blood T cells isolated from convalescent asymptomatic, moderate and severe COVID-19 patients. These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1-biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution.