Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective
Yuexiu Zhang, Michelle Chamblee, Jiayu Xu, Panke Qu, Mohamed M. Shamseldin, Sung J. Yoo, Jack Misny, Ilada Thongpan, Mahesh KC, Jesse M. Hall, Yash Gupta, John P. Evans, Mijia Lu, Chengjin Ye, Cheng Chih Hsu, Xueya Liang, Luis Martínez‐Sobrido, Jacob S. Yount, Prosper N. Boyaka, Shan‐Lu Liu, Purnima Dubey, Mark E. Peeples, Jiànróng Lǐ
Abstract
Abstract 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.