A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern

Author:

Xu Jiayu1,Zhang Yuexiu1ORCID,Qu Panke1,Shamseldin Mohamed M.23,Yoo Sung J.1ORCID,Misny Jack4,Thongpan Ilada4,KC Mahesh4ORCID,Hall Jesse M.2,Evans John P.1ORCID,Eltobgy Mostafa2ORCID,Lu Mijia1,Ye Chengjin5ORCID,Chamblee Michelle1,Liang Xueya1,Martinez-Sobrido Luis5ORCID,Amer Amal O.26ORCID,Yount Jacob S.26,Boyaka Prosper N.16ORCID,Peeples Mark E.467ORCID,Liu Shan-Lu1268ORCID,Dubey Purnima26ORCID,Li Jianrong16ORCID

Affiliation:

1. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210

2. Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210

3. Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Helwan 11795, Egypt

4. Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205

5. Department of Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227

6. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210

7. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210

8. Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210

Abstract

As SARS-CoV-2 variants of concern (VoCs) that evade immunity continue to emerge, next-generation adaptable COVID-19 vaccines which protect the respiratory tract and provide broader, more effective, and durable protection are urgently needed. Here, we have developed one such approach, a highly efficacious, intranasally delivered, trivalent measles-mumps-SARS-CoV-2 spike (S) protein (MMS) vaccine candidate that induces robust systemic and mucosal immunity with broad protection. This vaccine candidate is based on three components of the MMR vaccine, a measles virus Edmonston and the two mumps virus strains [Jeryl Lynn 1 (JL1) and JL2] that are known to provide safe, effective, and long-lasting protective immunity. The six proline-stabilized prefusion S protein (preS-6P) genes for ancestral SARS-CoV-2 WA1 and two important SARS-CoV-2 VoCs (Delta and Omicron BA.1) were each inserted into one of these three viruses which were then combined into a trivalent “MMS” candidate vaccine. Intranasal immunization of MMS in IFNAR1 −/− mice induced a strong SARS-CoV-2-specific serum IgG response, cross-variant neutralizing antibodies, mucosal IgA, and systemic and tissue-resident T cells. Immunization of golden Syrian hamsters with MMS vaccine induced similarly high levels of antibodies that efficiently neutralized SARS-CoV-2 VoCs and provided broad and complete protection against challenge with any of these VoCs. This MMS vaccine is an efficacious, broadly protective next-generation COVID-19 vaccine candidate, which is readily adaptable to new variants, built on a platform with a 50-y safety record that also protects against measles and mumps.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | National Institutes of Health

HHS | NIH | National Cancer Institute

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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