Del Fresno, CarlosGarcía-Arriaza, JuanMartínez-Cano, SaraiHeras-Murillo, IgnacioJarit-Cabanillas, AitorAmores-Iniesta, JoaquinBrandi, PaolaDunphy, GillianSuay-Corredera, CarmenPricolo, Maria RosariaVicente, NataliaLópez-Perrote, AndrésCabezudo, SofíaGonzález-Corpas, AnaLlorca, OscarAlegre-Cebollada, JorgeGaraigorta, UrtziGastaminza, PabloEsteban, MarianoSancho, David2022-10-252022-10-252021-11Front Immunol . 2021 Nov 18;12:748103http://hdl.handle.net/20.500.12105/15094COVID-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.engVoRhttp://creativecommons.org/licenses/by/4.0/Administration, MucosalAnimalsAntibodies, ViralBacteriaCD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesImmunity, HeterologousImmunity, InnateImmunogenicity, VaccineImmunoglobulin AImmunologic FactorsMiceSARS-CoV-2VaccinationAtribución 4.0 Internacional348679741274810310.3389/fimmu.2021.7481031664-3224Frontiers in immunologyopen access