Development of a safe and effective RBD-based vaccine against MERS-CoV

In response to the NIH's call for countermeasures to prevent emerging infectious diseases, we willdevelop, test and manufacture the Middle East Respiratory Syndrome Coronavirus receptor binding protein(MERS-CoV RBD) vaccine as an innovative countermeasure. According to the WHO, MERS-CoV remains aserious global concern mainly due to its potential to cause explosive outbreaks with substantial socio-economicconsequences, if not controlled adequately. Therefore, an effective and safe vaccine is urgently needed. Wehave identified and produced at bench-scale a highly promising lead candidate vaccine antigen for MERS-CoVcomprised of the RBD of the spike (S) protein. This domain contains the major neutralizing epitopes and caninduce potent neutralizing antibody response and protection in animals against infection without causingantibody-dependent enhancement or eosinophilic pathology. Our MERS-CoV RBD is the leading vaccinecandidate because it elicits high titers of anti-RBD neutralizing antibodies, the major correlate of protectionagainst MERS CoV infection. It induces protection without eosinophilic immunopathology, the majordetrimental effect of vaccines that employ whole virus or full-length S protein constructs, and it is stable,enabling stockpiling for emergency use. To rapidly translate these laboratory findings, Texas Children'sHospital Center for Vaccine Development at Baylor College Medicine established a new Coronavirus VaccineDevelopment Product Development Partnership (CoV-PDP) comprised of New York Blood Center, UTMBGalveston, and PnuVax Ltd., as its industrial manufacturing partner. We have a proven track record ofinnovative and high impact scientific publications, the ability to develop and technology transfer recombinantprotein vaccines under cGMP, as well as experience with IND preparations and regulatory filings with the U.S.FDA. Through previous NIAID NIH funding the CoV-PDP has already developed and manufactured a SARS-CoV RBD vaccine. The specific aims of this application are: (1) Process development, pilot scale production,technology transfer and cGMP manufacture of the MERS-CoV RBD vaccine. Activities include scale-up ofexpression, assay development, formulation, and stability profiling, followed by technology transfer to PnuVax,where an engineering run and two cGMP production runs will be conducted. (2) Assessment of functionalityand antigenicity of MERS-CoV RBD vaccine, and demonstration of its immunogenicity in wild-type mice.Specifically, we will evaluate the vaccine for its functionality and antigenicity, followed by optimizing the antigendoses for optimal immunogenicity, including RBD-specific antibody and T-cell responses, as well as long-termimmune responses. (3) Evaluation of the immunogenicity, efficacy and safety of the vaccine in young and agedhDPP4-trensgenic mice well-known to be highly permissive to MERS-CoV infection and disease, followed bytesting in non-human primates. At the conclusion of these studies, cGMP-grade material will be available forGLP toxicology studies, IND preparation/submission, and first-in-humans clinical testing.