A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern
Jiayu Xu, Yuexiu Zhang, Panke Qu, Mohamed M. Shamseldin, Sung J. Yoo, Jack Misny, Ilada Thongpan, Mahesh KC, Jesse M. Hall, John P. Evans, Mostafa Eltobgy, Mijia Lu, Chengjin Ye, Michelle Chamblee, Xueya Liang, Luis Martínez‐Sobrido, Amal O. Amer, Jacob S. Yount, Prosper N. Boyaka, Mark E. Peeples, Shan‐Lu Liu, Purnima Dubey, Jiànróng Lǐ
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.