Carlos del Fresno, Juan García-Arriaza, Sarai Martínez-Cano, Ignacio Heras-Murillo, Aitor Jarit-Cabanillas, Joaquín Amores-Iniesta, Paola Brandi, Gillian Dunphy, Carmen Suay-Corredera, Maria Rosaria Pricolo, Natalia Vicente, Andrés López-Perrote, Sofía Cabezudo, Ana González-Corpas, Oscar Llorca, Jorge Alegre-Cebollada, Urtzi Garaigorta, Pablo Gastaminza, Mariano Esteban, and David Sancho.

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.

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