AUTHOR=del Fresno Carlos, García-Arriaza Juan, Martínez-Cano Sarai, Heras-Murillo Ignacio, Jarit-Cabanillas Aitor, Amores-Iniesta Joaquín, Brandi Paola, Dunphy Gillian, Suay-Corredera Carmen, Pricolo Maria Rosaria, Vicente Natalia, López-Perrote Andrés, Cabezudo Sofía, González-Corpas Ana, Llorca Oscar, Alegre-Cebollada Jorge, Garaigorta Urtzi, Gastaminza Pablo, Esteban Mariano, Sancho David TITLE=The Bacterial Mucosal Immunotherapy MV130 Protects Against SARS-CoV-2 Infection and Improves COVID-19 Vaccines Immunogenicity JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/articles/10.3389/fimmu.2021.748103 DOI=10.3389/fimmu.2021.748103 ISSN=1664-3224 ABSTRACT=COVID-19-specific vaccines are efficient prophylactic weapons against SARS-CoV-2 virus. However, boosting innate responses may represent an innovative way to immediately fight future emerging viral infections or boost vaccines. MV130 is a mucosal immunotherapy, based on a mixture of whole heat-inactivated bacteria, that has shown clinical efficacy against recurrent viral respiratory infections. Herein, we show that the prophylactic intranasal administration of this immunotherapy confers heterologous protection against SARS-CoV-2 infection in susceptible K18-hACE2 mice. Furthermore, in C57BL/6 mice, prophylactic administration of MV130 improves the immunogenicity of two different COVID-19 vaccine formulations targeting the SARS-CoV-2 spike (S) protein, inoculated either intramuscularly or intranasally. Independently of the vaccine candidate and vaccination route used, intranasal prophylaxis with MV130 boosted S-specific responses, including CD8+-T cell activation and the production of S-specific mucosal IgA antibodies. Therefore, the bacterial mucosal immunotherapy MV130 protects against SARS-CoV-2 infection and improves COVID-19 vaccines immunogenicity.