tetano
Editor, Senior Moderator
J Med Virol
. 2023 Mar 20.
doi: 10.1002/jmv.28687. Online ahead of print.
Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS-CoV-2 infection
Yuexiu Zhang[SUP] 1 [/SUP], Mijia Lu[SUP] 1 [/SUP], Ilada Thongpan[SUP] 2 [/SUP], Jiayu Xu[SUP] 1 [/SUP], Kc Mahesh[SUP] 2 [/SUP], Piyush Dravid[SUP] 2 [/SUP], Sheetal Trivedi[SUP] 2 [/SUP], Himanshu Sharma[SUP] 2 [/SUP], Xueya Liang[SUP] 1 [/SUP], Amit Kapoor[SUP] 2 3 4 [/SUP], Mark E Peeples[SUP] 2 3 4 [/SUP], Jianrong Li[SUP] 1 4 [/SUP]
Affiliations
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[SUP]-/-[/SUP] mice. IFNAR[SUP]-/-[/SUP] 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.
Keywords: Measles virus: Virus classification; SARS coronavirus: Virus classification; Vaccines/Vaccine strains: Disease control.
. 2023 Mar 20.
doi: 10.1002/jmv.28687. Online ahead of print.
Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS-CoV-2 infection
Yuexiu Zhang[SUP] 1 [/SUP], Mijia Lu[SUP] 1 [/SUP], Ilada Thongpan[SUP] 2 [/SUP], Jiayu Xu[SUP] 1 [/SUP], Kc Mahesh[SUP] 2 [/SUP], Piyush Dravid[SUP] 2 [/SUP], Sheetal Trivedi[SUP] 2 [/SUP], Himanshu Sharma[SUP] 2 [/SUP], Xueya Liang[SUP] 1 [/SUP], Amit Kapoor[SUP] 2 3 4 [/SUP], Mark E Peeples[SUP] 2 3 4 [/SUP], Jianrong Li[SUP] 1 4 [/SUP]
Affiliations
- PMID: 36941778
- DOI: 10.1002/jmv.28687
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[SUP]-/-[/SUP] mice. IFNAR[SUP]-/-[/SUP] 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.
Keywords: Measles virus: Virus classification; SARS coronavirus: Virus classification; Vaccines/Vaccine strains: Disease control.