Mucosal Vaccination Against SARS-CoV-2 Using Human Probiotic Spores as an Adjuvant Induces Potent Systemic and Mucosal Immunity.

: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. : Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic DG101 spores. : In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4 and CD8 T cells in the lungs. : All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission.