Document text
Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2023
Award: $2,798,848
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract - Core 3
The current SARS-CoV-2 pandemic is the third major pathogenic outbreak caused by a betaCoV in the last two
decades. Development of panbetacoronavirus (panbetaCoV) vaccines for group 2b and group 2c beta CoVs is
a major priority of this P01. In addition, this P01 will evaluate alphavirus replicons, modified mRNA-lipid
nanoparticles and protein nanoparticles as panbetaCoV vaccine platforms. Nonhuman primates (NHPs) such
as cynomolgus or rhesus macaques have been shown by the NHP Core 3 team to be excellent models of SARS-
CoV-2 acquisition. NHPs are important components of vaccine design and testing as they have anatomical,
physiological and immunological similarities to humans. The NHP Core 3 will support the P01 by achieving the
following Specific Aims: Aim 1. Test the protectivecapacityof panbetaCoVneutralizing antibodyvaccines
using cynomolgus or rhesus monkeys as animal models. Down-selected B cell vaccines derived from
Projects 1, 2, 3 or 4 will be tested in NHP models. We hypothesize that macaques will be as excellent models
of bat or pangolin CoV acquisition as they are for human prototype group 2b CoVs (SARS-CoV-1 and 2) and
group 2c human virus, MERS. Aim 2. Test the protective capacity of panbetaCoV T cell basedvaccines
using cynomolgus or rhesus monkeys as animal models. CD8 T cell responses have been shown to be a
component of immune correlates of protection from SARS-CoV-2 in rhesus macaques. The hypothesis here is
that a T cell-targeted vaccine can synergize with B cell vaccines to improve protection with low neutralizing
antibody titers. Down-selected T cell vaccines derived from Project 4 will be tested in NHP models, whereT cell
responses will be assessed through a step-wise epitope-based approach using assays including IFN-γ-based
ELISpot, multi-parameter flow cytometry-based assays, and 10X genomics transcriptome analysis. Aim 3.
Monitor Vaccine Associated Enhancement of Disease (VAED) in macaques by panbetaCoV vaccines.
We will monitor vaccinated macaques for lung pathology and enhancedBAL cytokines and lung CoV PFU. Thus,
NHP Core 3 will be an integral component of this P01 and key to P01 success.
Terms: <Accreditation><Adjuvant><African Green Monkey><Alpha Virus><Alphavirus><Alum Adjuvant><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody titer measurement><Antigenic Determinants><Assay><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bats><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID test><COVID tests><Cell Body><Cells><Chiroptera><Chlorocebus aethiops><Chlorocebus sabaeus><Collaborations><Crab-Eating Macaque><Crab-Eating Monkey><Cynomolgus Monkey><Cynomolgus macaque><Data><Development><Disease><Disease Outbreaks><Disease Progression><Disorder><Epitopes><Evaluation><Exposure to><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Future><Genomics><Goals><Green Monkey><Group A Arboviruses><Helper Cells><Helper T-Cells><Helper T-Lymphocytes><Helper-Inducer T-Cells><Helper-Inducer T-Lymphocyte><Human><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><Immune><Immune Interferon><Immune Monitoring><Immunes><Immunity><Immunization><Immunochemical Immunologic><Immunologic><Immunologic Monitoring><Immunological><Immunological Monitoring><Immunologically><Immunologics><Immunomonitoring><Inducer Cells><Inducer T-Lymphocytes><Interferon Gamma><Interferon Type II><International><LYT3><Leadership><Letters><Lung><Lung Respiratory System><M fascicularis><M mulatta><M. fascicularis><M. mulatta><MERS><MERS coronavirus disease><MERS-CoV disease><Macaca><Macaca fascicularis><Macaca mulatta><Macaque><Messenger RNA><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><Monitor><NIH><National Institutes of Health><Outbreaks><P01 Mechanism><P01 Program><Pathogenicity><Physiologic><Physiological><Preclinical Testing><Program Project Grant><Program Research Project Grants><Proteins><Pulmonary Pathology><Replication Unit><Replicon><Research Program Projects><Rhesus><Rhesus Macaque><Rhesus Monkey><SARS Virus><SARS corona virus><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-1><SARS-Related Coronavirus><Sampling><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><T cell response><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><TLR7><TLR7 gene><Testing><Time><Toll-Like Receptor 7><United States National Institutes of Health><Vaccinated><Vaccine Design><Vaccines><Viral Diseases><Virus><Virus Diseases><accredited><alum><aluminum sulfate><animal coronavirus><antibody titering><beta CoV><beta coronavirus><beta coronavirus vaccine><betaCoV><betacoronavirus><betacoronavirus vaccine><coronavirus disease test><coronavirus disease tests><coronavirus test><coronavirus tests><cytokine><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><evaluate vaccines><expectation><flow cytophotometry><global gene expression><global transcription profile><immunogenicity><immunopathology><improved><lFN-Gamma><lipid based nanoparticle><lipid nanoparticle><lung pathology><mRNA><model of animal><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><non-human primate><nonhuman primate><panbetaCoV vaccine><pandemic><pandemic disease><pleiotropic effect><pleiotropism><pleiotropy><pre-clinical><pre-clinical testing><preclinical><prototype><pulmonary><response><severe acute respiratory syndrome-CoV><success><synergism><test for COVID><thymus derived lymphocyte><transcriptome><vaccine antibodies><vaccine candidate><vaccine development><vaccine efficacy><vaccine evaluation><vaccine induced antibodies><vaccine platform><vaccine screening><vaccine testing><vaccine-induced antibodies><viral infection><virus infection><virus-induced disease><β CoV><β coronavirus><β coronavirus vaccine><βCoV>