biostudies-literatureZhang YU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Cancer InstituteNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)Division of Cancer Prevention, National Cancer InstituteNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)U.S. Department of Health & Human Services | National Institutes of Health5589https://www.ebi.ac.uk/biostudies/studies/S-EPMC11222507biostudies-literatureUnknown15(1)As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1^-/- mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immuniNature communicationsThree SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective.PMC11222507P01 AI112524AI145144R01 AI090060R01 AI157205P01 AI175399AI42733R01 AI130110AI093848R21 AI180667T32 AI165391AI112524R01 HL168501AI157205U54CA260582T32AI165391R01 AI093848AI175399U19 AI142733AI090060U54 CA260582R01 AI145144Hall JMYount JSThongpan IGupta YAMartinez-Sobrido LLi JLiang XKc MYe CEvans JPLiu SLPeeples MEXu JYoo SJHsu CCQu PLu MChamblee MZhang YDubey PShamseldin MMMisny JBoyaka PNfalseThree SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective.As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1^-/- mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immuni2024-01-01T00:00:00Z2024 Jul2026-07-15T09:55:35.089Z2025-04-04T12:21:57.787ZS-EPMC112225073896106310.1038/s41467-024-49443-2