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

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.

Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective

“…Because B.1.1.7 and B.1.617.2 are antigenically similar to the SARS-CoV-2 WA1, the benefit of combining B.1.1.7, B.1.617.2, and WA1 spikes in a trivalent vaccine may be limited. Importantly, we recently found that a trivalent vaccine containing BA.1, B.1.617.2, and WA1 spikes generated broad NAb against WA1, B.1.617.2, and Omicron BA.1 and BA4/5 VoCs whereas the monovalent vaccine containing BA.1 spike induced antibodies that only neutralize the homologous BA.1 virus, not the heterologous viruses 51 . Because Omicron BA.1 is antigenically far from WA1 and B.1.617.2, a trivalent vaccine that contains the spike of BA.1 may be capable of inducing more broadly NAbs.…”