Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS-CoV-2 infection.
Journal of medical virology(2023)
Abstract
Measles virus (MeV) has been an excellent vector platform for delivering vaccines against many pathogens because of its high safety and efficacy, and induction of long-lived immunity. Early in the COVID-19 pandemic, a recombinant MeV (rMeV) expressing the prefusion full-length spike protein stabilized by two prolines (TMV-083) was developed and tested in phase 1 and 1/2 clinical trials but was discontinued because of insufficient immunogenicity and a low seroconversion rate in adults. Here, we compared the immunogenicity of rMeV expressing a soluble prefusion spike (preS) protein stabilized by two prolines (rMeV-preS-2P) with a rMeV expressing a soluble preS protein stabilized by six prolines (rMeV-preS-6P). We found that rMeV-preS-6P expressed approximately 5 times more preS than rMeV-preS-2P in cell culture. Importantly, rMeV-preS-6P induced 30-60 and 6 times more serum IgG and neutralizing antibody than rMeV-preS-2P, respectively, in IFNAR mice. IFNAR mice immunized with rMeV-preS-6P were completely protected from challenge with a mouse adapted SARS-CoV-2 whereas those immunized with rMeV-preS-2P were partially protected. In addition, hamsters immunized with rMeV-preS-6P were completely protected from the challenge with a Delta variant of SARS-CoV-2. Our results demonstrate that rMeV-preS-6P is significantly more efficacious than rMeV-preS-2P, highlighting the value of using preS-6P as the antigen for developing vaccines against SARS-CoV-2. This article is protected by copyright. All rights reserved.
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Key words
Measles virus: Virus classification,SARS coronavirus: Virus classification,Vaccines/Vaccine strains: Disease control
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