Document text
Principal Investigator: Viviana A Simon
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2023
Award: $1,041,898
Funding agency: National Institute of Allergy and Infectious Diseases
The SARS-CoV-2 pandemic represents an exceptional public health crisis highlighting the need for better
understanding of the mechanisms controlling broadly protective immune responses and generating
vaccine candidates able to elicit such responses. The program project entitled “Programming Long-lasting
Immunity to Coronaviruses (PLUTO)” proposes a comprehensive research plan towards designing pan-
sarbecovirus and pan-betacoronavirus vaccines with broad protection by applying in-depth B cell
characterization in the context of coronavirus immune histories imprinted by successive vaccinations
and/or infections. Two complementary research projects will establish correlates of robust, durable
and protective coronavirus humoral immunity (Project 1) as well as design and test efficacy of viral
variant-proof pan-sarbecovirus and pan-betacoronavirus vaccines (Project 2). The Cores will synergize with
the two research projects to support the successful completion of the research aims. The Administrative
Core will manage the consortium, coordinate cross-project activities, and create the structure and
environment needed to accomplish PLUTO's goals. The Antibody Core will develop large panels of
recombinant monoclonal antibodies (mAbs) against coronavirus spike proteins to define specificity and
breath of immune responses elicited by coronavirus infections and/or vaccinations in humans and animal
models. The Animal Model Core will provide a central resource with approvals, facilities, and expertise
to assess efficacy of broadly cross-reactive coronavirus antibodies and vaccines in robust pre-clinical
models against a spectrum of coronaviruses, including Select Agents. The Research Projects will
collaborate with each other and with the Antibody and Animal Model Cores, coordinated by the
Administrative Core. Project 1 will focus on defining B cell responses to coronavirus infection and
vaccination. In Project 1, we will pair exceptionally unique clinical specimens with our in-depth
interrogation of B cell response dynamics at the single cell level and specificity at atomic resolution to
provide a robust platform for identifying correlates of protective immunity. The resulting structural data will
provide key information towards the development of a “universal” coronavirus vaccine (in collaboration with
Project 2). A multidisciplinary team of scientists from five institutions who have an outstanding track
record of working collaboratively will conduct the proposed studies. The integrated and synergistic
activities across Projects and Cores will drive the successful completion of the program project's
ambitious research agenda, enabling achievement of the long-term PLUTO goal of developing variant-proof
pan-sarbecovirus and pan-betacoronavirus vaccines. These findings will contribute to curbing the current
SARS-CoV-2 pandemic and mitigate the risk of future pandemics with coronaviruses.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Achievement><Achievement Attainment><Activities of Daily Living><Activities of everyday life><Address><Affect><Affinity><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antibody Specificity><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><B.1.1.529><B.1.351><B.1.617.2><Blood><Blood Plasma Cell><Blood Reticuloendothelial System><Bone Marrow><Bone Marrow Reticuloendothelial System><COVID crisis><COVID epidemic><COVID pandemic><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 vaccination><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 public health crisis><COVID19 vaccination><COVID19 vaccine><COVID19 virus><Cell Body><Cell Isolation><Cell Segregation><Cell Separation><Cell Separation Technology><Cells><Clinical><Clinical Treatment Moab><Clone Cells><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Collaborations><Complex><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Coronavirus glycoprotein S><Coronavirus spike protein><Data><Delta variant><Development><Environment><Epitope Mapping><Event><Exposure to><Funding><Future><Germinal Center><Goals><History><Human><Humoral Immunities><IRB><IRBs><Immune><Immune response><Immune system><Immunes><Immunity><Immunization><Immunological response><Individual><Infection><Institution><Institutional Review Boards><Knowledge><Length of Life><Licensing><Longevity><Memory B Cell><Memory B-Lymphocyte><Mice><Mice Mammals><Microanatomy><Microscopic Anatomy><Modern Man><Monoclonal Antibodies><Murine><Mus><New York City><Omicron variant><PBMC><Peripheral Blood Mononuclear Cell><Plasma Cells><Plasmacytes><Pre-Clinical Model><Preclinical Models><Public Health><R-Series Research Projects><R01 Mechanism><R01 Program><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><Recombinants><Recording of previous events><Research><Research Grants><Research Project Grants><Research Projects><Research Resources><Research Specimen><Resolution><Resources><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.1.529><SARS-CoV-2 B.1.351><SARS-CoV-2 B.1.617.2><SARS-CoV-2 beta><SARS-CoV-2 delta><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 omicron><SARS-CoV-2 omicron variant><SARS-CoV-2 pandemic><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 vaccine><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><Sarbecovirus><Scientist><Series><Serology><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 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-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><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 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><South Africa strain><South Africa variant><South African strain><South African variant><Specificity><Specimen><Structure><Structure of germinal center of lymph node><Surface><Vaccination><Vaccine Design><Vaccinee><Vaccines><Variant><Variation><Viral><Wuhan coronavirus><antibody-based immunity><beta coronavirus vaccine><betacoronavirus vaccine><cell sorting><cohort><corona virus><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus S protein><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 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus of pandemic concern><coronavirus of pandemic potential><coronavirus spike glycoprotein><coronavirus vaccination><coronavirus vaccine><coronavirus with pandemic potential><cross reactivity><daily living function><daily living functionality><design><designing><determine efficacy><developmental><draining lymph node><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><efficacy testing><evaluate efficacy><examine efficacy><experience><flexibility><flexible><functional ability><functional capacity><future pandemic><hCoV19><histories><host response><human model><immune system response><immunogenic><immunoresponse><imprint><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><innovate><innovation><innovative><life span><lifespan><lymph organ><lymphatic organ><lymphoid organ><mAbs><mRNA immunization><mRNA vaccination><mRNA vaccine><mRNA-based vaccine><model of animal><model of human><monoclonal Abs><multidisciplinary><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><next pandemic><novel><omicron variant of COVID-19><omicron variant of SARS-CoV-2><pan CoV vaccine><pan coronavirus vaccine><panCoV vaccine><panbetaCoV vaccine><pancoronavirus vaccine><pandemic><pandemic concern><pandemic coronavirus><pandemic disease><pandemic potential><pandemic risk><pandemic threat><pandemic threat coronavirus><participant enrollment><patient enrollment><plasmocyte><polyclonal antibody><programs><regional lymph node><resolutions><respiratory pathogen><response><risk mitigation><seasonal coronavirus><seasonal human coronavirus><severe acute respiratory syndrome coronavirus 2 B.1.1.529><severe acute respiratory syndrome coronavirus 2 B.1.351><severe acute respiratory syndrome coronavirus 2 B.1.617.2><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><synergism><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><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination against COVID-19><vaccination against COVID19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus><vaccination against coronavirus disease 2019><vaccination study><vaccination trial><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 for novel coronavirus><vaccine study><vaccine trial><variants of concern><ward><β coronavirus vaccine>