Mucosal Vaccination Against SARS-CoV-2 Using Human Probiotic <i>Bacillus subtilis</i> Spores as an Adjuvant Induces Potent Systemic and Mucosal Immunity

<b>Background/Objectives</b>: 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. <b>Methods</b>: Here, we evaluated an intranasal (IN) vac...

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Main Authors: Raul Ramos Pupo, Laura M. Reyes Diaz, Gisela M. Suarez Formigo, Yusnaby Borrego Gonzalez, Miriam Lastre Gonzalez, Danay Saavedra Hernandez, Tania Crombet Ramos, Belinda Sanchez Ramirez, Roberto Grau, Niels Hellings, Piet Stinissen, Oliver Perez, Jeroen F. J. Bogie
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/772
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Summary:<b>Background/Objectives</b>: 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. <b>Methods</b>: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic <i>Bacillus subtilis</i> DG101 spores. <b>Results</b>: 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<sup>+</sup> and CD8<sup>+</sup> T cells in the lungs. <b>Conclusions</b>: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic <i>B. subtilis</i> spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission.
ISSN:2076-393X