Christoph Wirblich
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.
Authors
CHRISTOPHER COLEMAN CHRISTOPHER.COLEMAN@NOTTINGHAM.AC.UK
Assistant Professor of Infection Immunology
Drishya Kurup
Tara S. Abraham
John G. Bernbaum
Peter B. Jahrling
Lisa E. Hensley
Reed F. Johnson
Matthew B. Frieman
Matthias J. Schnell
Contributors
Adolfo García-Sastre
Editor
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 |
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