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Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2021
Award: $17,521,953
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract - Overall
Compared to SARS-CoV-1 and MERS, the current SARS-CoV-2 virus is highly transmissible and to date has
caused over 85,000,000cases worldwidewith over 1,800,000 deaths. With an endemic population of multipleother
strains of CoVs in bats, rodents with intermediate hosts, civets and pangolins, and because of the ability of CoVs
to recombine, it is a certainty that new CoVs with infectious potential for humans will cause future human
pandemics. To address this problem in a focused and integrated way, this P01 team of virologists, immunologists,
computational biologists, structural biologists, biophysicists, evolutionary biologists, and traditional vacci nologists
will develop panbetacoronavirus (panbetaCoV) vaccines, including Merbecoviruses (group 2c), which gave rise to
MERS, and Sarbecoviruses (group 2b), which gave rise to SARS CoV-1 and SARS CoV-2, the three most deadly
betaCoV human outbreaks. The Significance of this grant is that it will provide for panbetaCoV vaccines for future
epidemics that can be immediately available at the onset of a betaCoV pandemic, avoiding much of the human
tragedy and social disruption caused by a pandemic. The Overall Specific Aims of the P01 are:
Aim 1. Develop and characterize immunogenicity of PanbetaCoV Sarbecovirus (Group 2b) vaccine candidates.
Aim 2. Determine Group 2b vaccine candidate protection capacity against group 2b panel of viruses.
Aim 3. Develop PanbetaCoVMerbecovirus (group2c) vaccine candidates, determinetheir immunogenicity, cross-
reactivity with other betaCoVs and protection capacity against group 2c panel of viruses.
This program project grant includes four projects. Project 1 will design vaccines in alphavirus replicon particle
(VRP) vaccine system, develop and test P01 vaccines in their unique mouse CoV challenge models. Project 2
will use structure-based molecular modeling and monomer and multimer nanoparticle spike protein designs and
test in wild-type mouse models. Project 3 will both design CoV vaccines and test vaccine designs expressed as
mRNAs in liquid nanoparticles (LNPs). Project 4 will computationally design B and T cell panbetaCoV vaccines.
This P01 proposes three Cores: an Administrative Core, a Biocontainment and Immune Monitoring Core,
and a Non-human Primate Core. Work in this P01 will provide panbetaCoV vaccines to protect against escape
mutants of SARS-CoV-2 in the current epidemic, and will be available to protect society against new betaCoVs
that might emerge to infect humans in the future.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Aerosols><Alpha Virus><Alphavirus><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antigenic Determinants><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bats><Binding Determinants><COVID-19><COVID-19 virus><COVID19><COVID19 virus><CV-19><CV19><Cessation of life><Chiroptera><Civet Cats><Civets><CoV emergence><CoV-2><CoV2><Cold Chains><Combination Vaccines><Combined Vaccines><Coronaviridae><Coronavirus><Crab-Eating Macaque><Crab-Eating Monkey><Cynomolgus Monkey><Cynomolgus macaque><Death><Development><Disease><Disease Outbreaks><Disorder><Dose><Epidemic><Epitopes><Escape Mutant><Event><Future><Genetic Alteration><Genetic Change><Genetic defect><Goals><Grant><Group A Arboviruses><Human><Immune><Immune Monitoring><Immune response><Immunes><Immunologic Monitoring><Immunological Monitoring><Immunological response><Immunologist><Immunomonitoring><Laboratories><Liquid substance><M fascicularis><M mulatta><M. fascicularis><M. mulatta><MERS><MERS coronavirus disease><MERS-CoV disease><Macaca><Macaca fascicularis><Macaca mulatta><Macaque><Measures><Messenger RNA><Mice><Mice Mammals><Middle East Respiratory Syndrome><Middle East Respiratory Syndrome CoV disease><Middle East Respiratory Syndrome coronavirus disease><Middle Eastern Respiratory Syndrome><Middle Eastern Respiratory Syndrome CoV disease><Middle Eastern Respiratory Syndrome coronavirus disease><Modeling><Modern Man><Molecular Modeling Nucleic Acid Biochemistry><Molecular Modeling Protein/Amino Acid Biochemistry><Molecular Models><Monitor><Murine><Mus><Mutate><Mutation><N-terminal><NH2-terminal><Nucleosides><Outbreaks><P01 Mechanism><P01 Program><Population><Program Project Grant><Program Research Project Grants><Protein Engineering><Proteins><Regimen><Replication Unit><Replicon><Research Program Projects><Research Resources><Resource Sharing><Resources><Rhesus Macaque><Rhesus Monkey><Rodent><Rodentia><Rodents Mammals><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Societies><Structural Biologist><Structure><System><T-Cells><T-Lymphocyte><Testing><Vaccination><Vaccine Design><Vaccines><Virus><Viverridae><Wild Type Mouse><Work><Wuhan coronavirus><base><beta CoV><beta coronavirus><beta coronavirus vaccine><betaCoV><betacoronavirus><betacoronavirus vaccine><corona virus><corona virus disease 2019><corona virus emergence><coronavirus disease 2019><coronavirus disease 2019 virus><coronavirus emergence><coronavirus vaccine><cross reactivity><design><designing><developmental><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><evaluate vaccines><fluid><genetic protein engineering><genome mutation><hCoV19><host response><immune system response><immunogen><immunogenicity><immunoresponse><lipid nanoparticle><liquid><mRNA><model of animal><model organism><molecular modeling><monomer><mouse model><murine model><nCoV><nCoV2><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><new CoV><new corona virus><new coronavirus><non-human primate><nonhuman primate><novel><novel CoV><novel corona virus><novel coronavirus><panbetaCoV vaccine><pandemic><pandemic disease><particle><programs><protective efficacy><protein design><receptor binding><receptor bound><respiratory><severe acute respiratory syndrome-CoV><social><thymus derived lymphocyte><vaccine against coronavirus><vaccine candidate><vaccine evaluation><vaccine screening><vaccine testing><wildtype mouse><zoonotic spillover><β CoV><β coronavirus><β coronavirus vaccine><βCoV>