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Principal Investigator: Pamela J Bjorkman
Organization: ROCKEFELLER UNIVERSITY
Fiscal Year: 2022
Award: $1,507,637
Funding agency: National Institute of Allergy and Infectious Diseases
Project 3: Summary/Abstract
SARS-CoV-2, a newly-emergent betacoronavirus in the sarbecovirus genus, resulted in a global pandemic in
2020, infecting millions and causing COVID-19 disease. Two other zoonotic betacoronaviruses, SARS-CoV (a
sarbecovirus) and MERS-CoV (a merbecovirus), also resulted in outbreaks within the last 20 years. SARS-like
viruses circulate in bats and serological surveillance of people living near caves where bats carry diverse
coronaviruses demonstrate direct transmission of SARS-like viruses with pandemic potential, suggesting a pan-
coronavirus vaccine is needed. In Project 3, the Bjorkman lab will use structural biology and biochemical
approaches to understand the neutralization mechanisms of antibodies (Abs) elicited in humans by SARS-CoV-
2 infection or vaccination and in experimental animals by immunization. In Aim 1, using 3D structures of Ab Fabs
bound to coronavirus spike (S) trimers, we will derive the structural correlates of neutralization/binding for
monoclonal Abs (mAbs) and polyclonal plasmas isolated in Project 1 by Dr. Nussenzweig from (i) humans
infected by SARS-CoV-2 after ~1 month, (ii) matured human Abs isolated ½ - 2 years after infection, (iii) humans
vaccinated against SARS-CoV-2 with the Moderna vaccine, and (iv) animals immunized with vaccine candidates
developed in Project 2 by Drs. Bieniasz and Hatziioannou or developed in this project's Aim 2 in the Bjorkman
laboratory. Aim 2 of this project will follow up on our lab's evaluations of the potential for cross-reactive antibody
responses to sarbecoviruses, for which we made homotypic nanoparticles presenting the receptor-binding
domain (RBD) of only SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal
betacoronaviruses (mosaic nanoparticles; 4-8 distinct RBDs). By combining results of functional analyses of Ab
neutralization derived from pseudotyped and authentic virus neutralization assays in collaboration with Dr. Rice
with structural analyses of Abs isolated from RBD-nanoparticle–injected mice, we will refine our nanoparticle
vaccine candidate(s) to increase their potential to protect against sarbecoviruses. Furthermore, we will develop
additional vaccine candidates against merbecoviruses and/or alphacoronaviruses that will be evaluated along
with the best pan-sarbecovirus vaccine in animal models of protection by Dr. Rice and/or our NIH collaborator,
Dr. Vincent Munster. This highly-integrated project has the potential to contribute to creation of vaccine(s) that
could avert future global pandemics.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><3-D structure><3-dimensional structure><3D structure><Abbreviations><Active Follow-up><Acute Nasopharyngitis><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><Antigenic Determinants><Assay><Bats><Binding><Binding Determinants><Bioassay><Biochemical><Biologic Assays><Biological Assay><Blood Plasma><COVID-19><COVID-19 antibody><COVID-19 infection><COVID-19 vaccination><COVID-19 virus><COVID19><COVID19 infection><COVID19 vaccination><COVID19 virus><CV-19><CV19><Chiroptera><Clinical Treatment Moab><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Collaborations><Common Cold><Complement><Complement Proteins><Complementarity Determining Regions><Complex><Complimentarity Determining Region><Coronaviridae><Coronavirus><Coronavirus glycoprotein S><Coronavirus spike protein><Cryo-electron Microscopy><Cryoelectron Microscopy><Crystallization><Disease><Disease Outbreaks><Disorder><ELISA><Electron Cryomicroscopy><Electron Microscopy><Enzyme-Linked Immunosorbent Assay><Epitope Mapping><Epitopes><Evaluation><Future><Human><Hypervariable Loop><Hypervariable Regions><Ig Somatic Hypermutation><Immunization><Immunize><Immunoglobulin Hypervariable Region><Immunoglobulin Somatic Hypermutation><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunostimulation><Infection><Laboratories><Light><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Maps><Merbecovirus><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><Modern Man><Molecular Interaction><Molecular Sieve Chromatography><Monoclonal Antibodies><Mosaicism><Murine><Mus><NIH><National Institutes of Health><Negative Staining><Outbreaks><Persons><Photoradiation><Plasma><Plasma Serum><Publications><Resolution><Reticuloendothelial System, Serum, Plasma><Rice><SARS><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV disease><SARS-CoV-1><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 infection><SARS-CoV-2 vaccination><SARS-CoV2><SARS-CoV2 antibody><SARS-CoV2 infection><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><Sarbecovirus><Scientific Publication><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><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><Severe Acute Respiratory Syndrome CoV 2><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><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 infection><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome related corona virus 2><Size Exclusion Chromatography><Structure><Surface Plasmon Resonance><Testing><Transmission><United States National Institutes of Health><Vaccinated><Vaccination><Vaccines><Virus><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><active followup><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><beta CoV><beta coronavirus><betaCoV><betacoronavirus><convalescent plasma><corona virus><corona virus disease 2019><coronavirus S protein><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 infection><coronavirus disease 2019 vaccination><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus of pandemic concern><coronavirus of pandemic potential><coronavirus spike glycoprotein><coronavirus with pandemic potential><cross reactivity><cryo-EM><cryoEM><enzyme linked immunoassay><experiment><experimental research><experimental study><follow up><follow-up><followed up><followup><hCoV19><improved><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><mAbs><model of animal><model organism><mosaic disorders><mutant><nCoV2><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><pan CoV vaccine><pan coronavirus vaccine><panCoV vaccine><pancoronavirus vaccine><pandemic><pandemic coronavirus><pandemic disease><pandemic threat coronavirus><particle><receptor binding><receptor bound><response><serology surveillance><serosurveillance><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome-CoV><somatic hypermutation><structural biology><three dimensional structure><transmission process><universal CoV vaccine><universal coronavirus vaccine><vaccinate against COVID-19><vaccinate against COVID19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against COVID19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine candidate><zoonotic CoV><zoonotic coronavirus><β CoV><β coronavirus><βCoV>