Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS‐CoV‐2 infection

Zhang, Yuexiu; Lu, Mijia; Thongpan, Ilada; Xu, Jiayu; Kc, Mahesh; Dravid, Piyush; Trivedi, Sheetal; Sharma, Himanshu; Liang, Xueya; Kapoor, Amit; Peeples, Mark E.; Li, Jianrong

doi:10.1002/jmv.28687

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…We recently showed that preS stabilized by 6 prolines (preS-6P) ( 20 ) induced six to eight times higher NAbs than preS-2P ( 21 ) in MuV-JL2 ( 18 ) and MeV ( 22 ) vectors. Therefore, we inserted a codon-optimized preS-6P gene of the Delta variant into the P–M gene junction of the MuV-JL1 genome ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, all current COVID-19 vaccines utilize the native full-length S or preS-2P as the vaccine antigen (3) . Because preS-6P has much higher protein expression and is more stable compared to preS-2P, the use of preS-6P in vaccine design will significantly enhance the efficacy and longevity of immune responses ( 18 , 20 , 22 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

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

Xu,

Zhang,

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Xu,

Zhang,

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…However, the rMeV-based SARS-CoV-2 vaccine platform (V591) developed by Merck was announced to be discontinued in phase I and I/II clinical trials because of the insufficient immune responses and seroconversion rate [ 40 ]. Thus, they concluded that V591 was generally well tolerated but the immunogenicity was not sufficient for further development [ 41 ]. In addition, rMeV-preFS induced high levels of immune response compared with rMeV-S+SPD in hamsters.…”

Section: Discussionmentioning

confidence: 99%

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters

Yang,

Song,

Pei

et al. 2024

Viruses

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As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

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

Zhang,

Chamblee,

et al. 2024

Nat Commun

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As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1−/− mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.

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Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS‐CoV‐2 infection

Cited by 3 publications

References 36 publications

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

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

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters

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

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