%0 Journal Article
%T Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective.
%A Zhang Y
%A Chamblee M
%A Xu J
%A Qu P
%A Shamseldin MM
%A Yoo SJ
%A Misny J
%A Thongpan I
%A Kc M
%A Hall JM
%A Gupta YA
%A Evans JP
%A Lu M
%A Ye C
%A Hsu CC
%A Liang X
%A Martinez-Sobrido L
%A Yount JS
%A Boyaka PN
%A Liu SL
%A Dubey P
%A Peeples ME
%A Li J
%J Nat Commun
%V 15
%N 1
%D 2024 Jul 3
%M 38961063
%F 17.694
%R 10.1038/s41467-024-49443-2
%X 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 immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.