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Intranasal #measles virus– and #mumps virus–based #SARS-CoV-2 #vaccine candidates prevent SARS-CoV-2 infection and #transmission

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By G.M.



Significance

An intranasal vaccine offers many unique advantages over traditional intramuscular-delivered vaccines. Here, we developed SARS-CoV-2 Omicron XBB.1.5 spike-based monovalent and trivalent vaccines using the live attenuated measles virus (MeV) and mumps viruses (MuV) as vectors. Intranasal immunization of hamsters and mice with monovalent and trivalent vaccines induces robust and broadly neutralizing antibodies, mucosal IgA antibodies, and lung-resident memory T cells, providing complete protection of the lung and nasal turbinate against challenges with SARS-CoV-2 WA1 and Omicron subvariants XBB.1.5, EG.5, and JN.1. In addition, intranasal immunization efficiently blocks transmission of SARS-CoV-2 WA1 and Omicron XBB.1.5 among the hamsters by direct contact. Therefore, MeV- and MuV-based intranasal vaccines are highly promising next-generation COVID-19 vaccine candidates that can prevent virus infection and transmission.


Abstract

The emergence of immune-evasive SARS-CoV-2 Omicron subvariants highlights the need to develop a mucosal SARS-CoV-2 vaccine that can provide broad protection against virus infection and transmission. Here, we developed an intranasal monovalent SARS-CoV-2 vaccine expressing the six-proline-stabilized prefusion spike proteins (preS-6P) of Omicron XBB.1.5 based on the attenuated mumps virus (MuV) Jeryl Lynn (JL1) vaccine strain. We also developed an intranasal trivalent vaccine expressing the preS-6P of ancestral SARS-CoV-2 WA1 and two Omicron subvariants, BA.1 and XBB.1.5, using the attenuated measles virus (MeV) and MuV-JL1 and JL2 vaccine strains, respectively. Intranasal immunization of hamsters with the monovalent rMuV-JL1-XBB.1.5 or the trivalent vaccine induced high levels of neutralizing antibodies (NAbs) that efficiently neutralized Omicron subvariants XBB.1.5, EG.5, and JN.1, providing complete protection against these Omicron subvariants. Similar levels of Omicron XBB.1.5 NAbs were detected in monovalent rMuV-JL1-XBB.1.5 and trivalent vaccine groups even when hamsters had been preimmunized with the rMuV-JL2-WA1 vaccine, suggesting that both intranasal vaccines are effective in the presence of immune imprinting induced by the spike of SARS-CoV-2 WA1. Intranasal, but not subcutaneous, immunization generated high levels of S-specific mucosal IgA antibodies as well as lung-resident memory T cells in IFNAR1−/− mice. Finally, intranasal immunization with the trivalent vaccine efficiently blocked transmission of SARS-CoV-2 WA1 and Omicron XBB.1.5 among hamsters in a direct contact transmission setting. In summary, we have developed intranasal MeV and MuV-based trivalent vaccines that induce broad NAbs, robust mucosal immunity, and strong protection against both virus challenge and virus transmission.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/abs/10.1073/pnas.2506821122?af=R

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