One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus

Wirblich, Christoph; Coleman, Christopher M.; Kurup, Drishya; Abraham, Tara S.; Bernbaum, John G.; Jahrling, Peter B.; Hensley, Lisa E.; Johnson, Reed F.; Frieman, Matthew B.; Schnell, Matthias J.

Abstract

© 2017 American Society for Microbiology. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic.

Citation

Wirblich, C., Coleman, C. M., Kurup, D., Abraham, T. S., Bernbaum, J. G., Jahrling, P. B., …Schnell, M. J. (2017). One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus. Journal of Virology, 91(2), Article 02040-16. https://doi.org/10.1128/jvi.02040-16

• Journal Article Type: Article
• Acceptance Date: Oct 30, 2016
• Online Publication Date: Jan 3, 2017
• Publication Date: Jan 15, 2017
• Deposit Date: Dec 17, 2019
• Journal: Journal of Virology
• Print ISSN: 0022-538X
• Electronic ISSN: 1098-5514
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 91
• Issue: 2
• Article Number: 02040-16
• DOI: https://doi.org/10.1128/jvi.02040-16
• Public URL: https://nottingham-repository.worktribe.com/output/3589867
• Publisher URL: https://jvi.asm.org/content/91/2/e02040-16