Adjuvant-free intranasal T cell vaccine enhances protective mucosal immunity against SARS-CoV-2 3397

Abstract Description The emergence of SARS-CoV-2 variants, such as Omicron, has challenged current spike protein-based COVID-19 vaccines due to antibody evasion and waning immunity. T cell-mediated immunity, characterized by durability and the ability to target conserved epitopes, offers a promising alternative for broad and long-lasting protection. Here, we identified conserved and Omicron BA.1-specific CD8 T cell epitopes within the SARS-CoV-2 spike protein and evaluated their efficacy in murine models using a carrier-protein fusion strategy. Parenteral immunizations with a two-epitope vaccine significantly lowered lung viral load but only conferred protection in low-dose SARS-CoV-2 challenge and failed against high-dose challenge. Notably, intranasal boosting, with or without adjuvant, significantly enhanced mucosal resident memory T cell responses, conferring complete protection against high-dose SARS-CoV-2 infection. These findings highlight that T cell-inducing vaccines focusing on a few conserved epitopes can offer sufficient protection against SARS-CoV-2 variants and adjuvant-free intranasal boosting is a viable approach to enhance protection against respiratory viral threats. Funding Sources NIAID 1P01AI165072 Topic Categories Vaccines and Immunotherapy (VAC)