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 A. Gupta, John P. Evans, Mijia Lu, Chengjin Ye, Cheng Chih Hsu, Xueya Liang, Luis Martinez-Sobrido, Jacob S. Yount, Prosper N. Boyaka, Shan-Lu Liu, Purnima Dubey, Mark E. Peeples and Jianrong Li ()
Additional contact information
Yuexiu Zhang: The Ohio State University
Michelle Chamblee: The Ohio State University
Jiayu Xu: The Ohio State University
Panke Qu: The Ohio State University
Mohamed M. Shamseldin: College of Medicine, The Ohio State University
Sung J. Yoo: The Ohio State University
Jack Misny: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Ilada Thongpan: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Mahesh Kc: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Jesse M. Hall: College of Medicine, The Ohio State University
Yash A. Gupta: College of Medicine, The Ohio State University
John P. Evans: The Ohio State University
Mijia Lu: The Ohio State University
Chengjin Ye: Texas Biomedical Research Institute
Cheng Chih Hsu: The Ohio State University
Xueya Liang: The Ohio State University
Luis Martinez-Sobrido: Texas Biomedical Research Institute
Jacob S. Yount: College of Medicine, The Ohio State University
Prosper N. Boyaka: The Ohio State University
Shan-Lu Liu: The Ohio State University
Purnima Dubey: College of Medicine, The Ohio State University
Mark E. Peeples: Abigail Wexner Research Institute at Nationwide Children’s Hospital
Jianrong Li: The Ohio State University

Nature Communications, 2024, vol. 15, issue 1, 1-19

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.

Date: 2024
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DOI: 10.1038/s41467-024-49443-2

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