Tweet
Proc Natl Acad Sci U S A
. 2025 Aug 12;122(32):e2506821122.
doi: 10.1073/pnas.2506821122. Epub 2025 Aug 6. Intranasal measles virus- and mumps virus-based SARS-CoV-2 vaccine candidates prevent SARS-CoV-2 infection and transmission
Cheng Chih Hsu # 1 , Michelle Chamblee # 1 , Chengjin Ye # 2 , Mohamed M Shamseldin # 3 4 , Sung J Yoo # 1 , Pei Li # 1 , Yuexiu Zhang # 1 , Yajie Liu 1 , Jesse M Hall 3 , Jiayu Xu 1 , Hanson Miao 1 , Ilada Thongpan 5 , Mahesh K C 5 , Xueya Liang 1 , Jacob S Yount 2 5 , Mark E Peeples 5 6 7 , Prosper N Boyaka 1 6 , Purnima Dubey 3 6 , Luis Martinez-Sobrido 2 , Shan-Lu Liu 1 3 6 , Jianrong Li 1 6
Affiliations
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.
Keywords: SARS-CoV-2; intranasal vaccine; virus transmission.
. 2025 Aug 12;122(32):e2506821122.
doi: 10.1073/pnas.2506821122. Epub 2025 Aug 6. Intranasal measles virus- and mumps virus-based SARS-CoV-2 vaccine candidates prevent SARS-CoV-2 infection and transmission
Cheng Chih Hsu # 1 , Michelle Chamblee # 1 , Chengjin Ye # 2 , Mohamed M Shamseldin # 3 4 , Sung J Yoo # 1 , Pei Li # 1 , Yuexiu Zhang # 1 , Yajie Liu 1 , Jesse M Hall 3 , Jiayu Xu 1 , Hanson Miao 1 , Ilada Thongpan 5 , Mahesh K C 5 , Xueya Liang 1 , Jacob S Yount 2 5 , Mark E Peeples 5 6 7 , Prosper N Boyaka 1 6 , Purnima Dubey 3 6 , Luis Martinez-Sobrido 2 , Shan-Lu Liu 1 3 6 , Jianrong Li 1 6
Affiliations
- PMID: 40768351
- DOI: 10.1073/pnas.2506821122
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.
Keywords: SARS-CoV-2; intranasal vaccine; virus transmission.