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

Abstract

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.IMPORTANCE Rabies virus-based vectors have been proven to be efficient dual vaccines against rabies and emergent infectious diseases such as Ebola virus. Here we show that inactivated rabies virus particles containing the MERS-CoV S1 protein induce potent immune responses against MERS-CoV and RABV. This novel vaccine is easy to produce and may be useful to protect target animals, such as camels, as well as humans from deadly MERS-CoV and RABV infections. Our results indicate that this vaccine approach can prevent disease, and the RABV-based vaccine platform may be a valuable tool for timely vaccine development against emerging infectious diseases.

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

“…hDPP4 can be expressed in the lungs of mice using an adenovirus vector [10]. In this model, there is robust replication of MERS-CoV in the lungs of the transduced mice that can be detected by both plaque assay and MERS-CoV RNA expression [16]. Therefore, we used this model to test the MERS-CoV S nanoparticle vaccine in vivo.…”

Rabies-based vaccine induces potent immune responses against Nipah virus

“…12 Previous studies have shown additive immunity with subsequent vaccinations of rabies-vectored inactivated vaccines. 7,37,38,51 The studies described here demonstrate the potential for a RABV platform for the development of a safe and effective NiV vaccine.…”

Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches

“…Inactivated virus vaccines may cause harm due to incomplete attenuation or the capacity to induce lung immunopathology [49]. Viral-vector-based vaccines, on the other hand, provide a safer alternative and have been developed using modified vaccinia virus Ankara (MVA) [50,51,52 ], adenovirus (AdV) [53,54], measles virus (MeV) [55], rabies virus (RABV) [56], and Venezuelan equine encephalitis replicons (VRP) [26,57], all expressing MERS-S/S1 proteins. Additionally, VRP expressing the N protein have also been developed [27 ].…”