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Principal Investigator: PETER J HOTEZ
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2020
Award: $549,181
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract: In response to the NIH's call for countermeasures to prevent emerging infectious diseases, we will
develop, 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 a
serious global concern mainly due to its potential to cause explosive outbreaks with substantial socio-economic
consequences, if not controlled adequately. Therefore, an effective and safe vaccine is urgently needed. We
have identified and produced at bench-scale a highly promising lead candidate vaccine antigen for MERS-CoV
comprised of the RBD of the spike (S) protein. This domain contains the major neutralizing epitopes and can
induce potent neutralizing antibody response and protection in animals against infection without causing
antibody-dependent enhancement or eosinophilic pathology. Our MERS-CoV RBD is the leading vaccine
candidate because it elicits high titers of anti-RBD neutralizing antibodies, the major correlate of protection
against MERS CoV infection. It induces protection without eosinophilic immunopathology, the major
detrimental 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's
Hospital Center for Vaccine Development at Baylor College Medicine established a new Coronavirus Vaccine
Development Product Development Partnership (CoV-PDP) comprised of New York Blood Center, UTMB
Galveston, and PnuVax Ltd., as its industrial manufacturing partner. We have a proven track record of
innovative and high impact scientific publications, the ability to develop and technology transfer recombinant
protein 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 of
expression, 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 functionality
and 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 antigen
doses for optimal immunogenicity, including RBD-specific antibody and T-cell responses, as well as long-term
immune responses. (3) Evaluation of the immunogenicity, efficacy and safety of the vaccine in young and aged
hDPP4-trensgenic mice well-known to be highly permissive to MERS-CoV infection and disease, followed by
testing in non-human primates. At the conclusion of these studies, cGMP-grade material will be available for
GLP toxicology studies, IND preparation/submission, and first-in-humans clinical testing.
Terms: <Address><Alum Adjuvant><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><Antibody-Dependent Enhancement><Antigen Targeting><Antigenic Determinants><Antigens><Binding Determinants><Binding Proteins><Biophysics><Blood><Blood Reticuloendothelial System><CHO Cells><COVID><Canada><Case Fatality Rates><Children's Hospital><Chinese Hamster Ovary Cell><Clinical Evaluation><Clinical Testing><Clone Cells><CoV disease><CoV emergence><Collaborations><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Cyclic GMP><Data><Development><Disease Outbreaks><Dose><Emergencies><Emergency Situation><Emerging Communicable Diseases><Emerging Infectious Diseases><Engineering><Epitopes><Evaluation><Formulation><Funding><Future><Geographic Distribution><Grant><Guanosine Cyclic Monophosphate><Human><Immune><Immune response><Immunes><Immunity><Immunological response><Industrialization><Infection><Infectious Agent><Lab Findings><Laboratories><Laboratory Finding><Lead><Length><Licensure><Ligand Binding Protein><Ligand Binding Protein Gene><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Medical><Medicine><Mice><Mice Mammals><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome-CoV><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Modeling><Modern Man><Murine><Mus><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><New York><Outbreaks><Paper><Pathogenicity><Pathology><Pb element><Pediatric Hospitals><Peer Review><Population><Preclinical Testing><Preparation><Process><Production><Productivity><Protein Binding><Proteins><Public Health><Publications><Receptor Protein><Recombinant Proteins><Recombinants><Research><Running><SARS><SARS Virus><SARS corona virus><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV disease><SARS-Related Coronavirus><Safety><Saudi Arabia><Scientific Publication><Scientist><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><System><T cell response><Technology><Technology Transfer><Testing><Texas><Therapeutic Intervention><Toxicology><Transgenic Mice><Translating><Treatment Efficacy><United States National Institutes of Health><Universities><Vaccine Antigen><Vaccine Production><Vaccines><Virus><Wild Type Mouse><Work><Yeasts><aged><alum><aluminum sulfate><animal efficacy><assay development><base><biodefense><biophysical foundation><biophysical principles><biophysical sciences><bound protein><cGMP><cGMP production><cell bank><clinical research site><clinical site><clinical test><college><collegiate><comparative><corona virus><corona virus disease><coronavirus disease><coronavirus emergence><design><designing><develop a vaccine><development of a vaccine><developmental><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><experience><first in man><first-in-human><heavy metal Pb><heavy metal lead><host response><immunogen><immunogenicity><immunopathology><immunoresponse><infectious organism><innovate><innovation><innovative><intervention efficacy><intervention therapy><lead candidate><medical countermeasure><model of animal><model organism><mouse model><murine model><nCoV><neutralizing antibody><new CoV><new coronavirus><non-human primate><nonhuman primate><novel CoV><novel coronavirus><pre-clinical study><pre-clinical testing><preclinical study><prevent><preventing><product development><receptor><receptor binding><receptor bound><research clinical testing><respiratory virus><response><scale up><severe acute respiratory syndrome-CoV><socio-economic><socio-economically><socioeconomically><socioeconomics><stable cell line><therapeutic efficacy><therapeutically effective><therapy efficacy><vaccine candidate><vaccine development><vaccine formulation><vaccine safety><wildtype mouse>