Document text
Principal Investigator: YOSHIHIRO KAWAOKA
Organization: UNIVERSITY OF WISCONSIN-MADISON
Fiscal Year: 2021
Award: $7,000,324
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY
Most of the vaccines currently approved or in development against the pandemic SARS-CoV-2 (severe acute
respiratory syndrome coronavirus 2) virus target immunodominant, strain-specific epitopes in the SARS-CoV-2
spike (S) protein and are therefore not expected to confer protection against other coronaviruses. Accordingly,
the NIAID announced NOT-AI-21-002, which calls for the “development of prophylactic vaccines to provide
broad and durable protection against coronaviruses, especially SARS-CoV-2 and others with pandemic
potential”. In response to this call, we assembled the Pan-Coronavirus Vaccine (PanCoVac) consortium to
develop and test novel pan-coronavirus vaccines. Research Project 1 (RP1; Design and evaluation of pan-
CoV vaccines) uses two strategies to develop broadly protective coronavirus vaccines: (i) Focus immune
responses away from the immunodominant epitopes in the head region of S and towards the more conserved,
immune-subdominant epitopes in the stem region of S; and (ii) Refocus immune responses from the variable
immunodominant epitopes towards more conserved epitopes in the head region of S. For each strategy, several
innovative approaches will be used. Novel antigens will be presented by virus-like particles based on a self-
assembling bacteriophage coat protein (a highly immunogenic platform). The candidate vaccines will be tested
for their immunogenicity and protective efficacy against different coronaviruses in an animal model. Selected
candidates will be tested in a second animal model, and with an mRNA lipid nanoparticle platform. Additional
studies will test the durability of immune responses and the effect of vaccination on virus transmission. Samples
from vaccinated animals will be provided to Research Project 2 (RP2; Immunological responses to pan-CoV
vaccines) for a detailed assessment of B- and T-cell responses. First, RP2 will continue its ongoing efforts to
generate and characterize panels of SARS-CoV S-specific mAbs, which will be used in RP1 to help characterize
and prioritize vaccine candidates. Moreover, “Ig-omics”, which involves single-cell technologies allowing high-
throughput analysis of B-cell responses, phenotypes, immunoglobulin (Ig) repertoires and mAbs that react to
several coronaviruses (a technology developed by one of the RP2 investigators), will be used to characterize B
cell-mediated immunity and mAb specificity induced by the candidate vaccines. RP2 will also test (and compare
with data from a human cohort study) the ability of the candidate vaccines to elicit responses to cross-reactive
CD4 and CD8 T cell epitopes. In particular, recently developed novel methods will be used to characterize and
compare the T-cell repertoires upon infection and vaccination. An Administrative Core will oversee and manage
all financial and administrative aspects of the consortium. Our proposed research draws strength from a multi-
institutional team of experts in molecular virology, structural biology, nanobiotechnology, and B- and T-cell
immunology.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><Affinity><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><Antigenic Determinants><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bacteriophages><Binding Determinants><Blood Plasma Cell><Blood Serum><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 crisis><COVID epidemic><COVID pandemic><COVID-19 S protein><COVID-19 antigen><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccine><COVID-19 virus><COVID19 S protein><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 public health crisis><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccine><COVID19 virus><Capsid Proteins><Cell Mediated Immunology><Cell-Mediated Immunity><Cellular Immunity><Clinical Treatment Moab><CoV-2><CoV2><Coat Proteins><Cohort Studies><Complement><Complement Proteins><Concurrent Studies><Coronaviridae><Coronavirus><Data><Development><Epitopes><Evaluation><Face><Funding><Generations><Genes><Germinal Center><Goals><Golden Hamsters><Golden Syrian Hamsters><Grippe><HCoV><Head><Human><Immune><Immune Globulins><Immune response><Immunes><Immunization><Immunize><Immunodominant Antigenic Determinants><Immunodominant Determinants><Immunodominant Domains><Immunodominant Epitopes><Immunodominant Regions><Immunodominant Sites><Immunoglobulins><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunology><Immunostimulation><Individual><Infection><Influenza><Investigators><Japanese><Japanese Population><Knowledge><LYT3><Long-term cohort study><Longitudinal cohort study><Longterm cohort study><Maintenance><Memory B Cell><Memory B-Lymphocyte><Mesocricetus auratus><Messenger RNA><Methods><Mice><Mice Mammals><Mission><Modern Man><Modification><Molecular Virology><Monoclonal Antibodies><Murine><Mus><Mutate><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Phages><Phenotype><Plasma Cells><Plasmacytes><Population><Preventative vaccine><Prevention><Preventive vaccine><Property><Prophylactic vaccine><Proteins><Public Health><R-Series Research Projects><R01 Mechanism><R01 Program><Receptor Protein><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Researchers><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 antigen><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 antigen><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-CoV2 vaccine><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Sequence Homology><Serum><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><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 coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Specificity><Structure of germinal center of lymph node><Syrian Hamsters><T cell response><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><T8 Cells><T8 Lymphocytes><Technology><Testing><Transgenic Mice><United States National Institutes of Health><Vaccinated><Vaccination><Vaccines><Viral Coat Proteins><Viral Gene Products><Viral Gene Proteins><Viral Outer Coat Protein><Viral Proteins><Virus><Virus-like particle><Wild Type Mouse><Wuhan coronavirus><bacterial virus><base><bionano technology><bionanotechnology><combat><corona virus><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus disease 2019 S protein><coronavirus disease 2019 antigen><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus receptor><coronavirus vaccine><cross reactivity><design><designing><develop a vaccine><development of a vaccine><developmental><faces><facial><hCoV19><high throughput analysis><host response><human CoV><human corona virus><human coronavirus><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innovate><innovation><innovative><lipid nanoparticle><long term memory><longterm memory><mAbs><mRNA><model of animal><model organism><nCoV2><nano biotechnology><nanobiotechnology><neutralizing antibody><new approaches><new vaccines><next generation vaccines><novel><novel approaches><novel strategies><novel strategy><novel vaccines><pan CoV vaccine><pan coronavirus vaccine><pandemic><pandemic disease><plasmocyte><protective efficacy><receptor><response><severe acute respiratory syndrome coronavirus 2 antigen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome-CoV><single cell technology><stem><structural biology><thymus derived lymphocyte><universal CoV vaccine><universal coronavirus vaccine><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine against coronavirus><vaccine candidate><vaccine development><vaccine for novel coronavirus><vaccine formulation><viral transmission><virus protein><virus transmission><virus-like nanoparticles><viruslike particle><wildtype mouse><zoonotic CoV><zoonotic coronavirus>