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

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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.
Funding Information
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (R01AI090060)
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (P01 AI112524)
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (P01 AI112524)
  • HHS | National Institutes of Health (U19AI42733)
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (R01AI145144)
  • HHS | National Institutes of Health (R01AI157205)
  • HHS | NIH | National Cancer Institute (U54CA260582)
  • HHS | National Institutes of Health (R01AI153829)

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