One-Health: A safe, efficient, dual-use vaccine for humans and animals against middle east respiratory syndrome coronavirus and rabies virus
JournalJournal of Virology
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractMiddle 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.
SponsorsThis work was supported in part by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research, the NIAID Division of Clinical Research, NIAID grant R01AI105204 to M.J.S., NIAID grant R01AI 5R01AI095569 to M.B.F., and the Jefferson Vaccine Center. This work was funded in part through Battelle Memorial Institute's prime contract with the NIAID under contract no. HHSN272200700016I. A subcontractor to Battelle Memorial Institute who performed this work is J.G.B., an employee of Tunnell Government Services, Inc. This work utilized the Bioimaging Shared Resource of the Sidney Kimmel Cancer Center (NCI 5 P30 CA-56036).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85008689569&doi=10.1128%2fJVI.02040-16&partnerID=40&md5=432990f6567fab1d7edb93cb23e8e38b; http://hdl.handle.net/10713/12397