Document text
Principal Investigator: Paul D. Bieniasz
Organization: ROCKEFELLER UNIVERSITY
Fiscal Year: 2023
Award: $4,259,011
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT-OVERALL
The recurrent emergence of coronaviruses from animal reservoirs, and the resulting COVID19 pandemic,
necessitates the development of interventions that can target diverse pandemic-threat coronaviruses.
Vaccines are among the most powerful means for mitigating viral epidemics but require significant breadth to
maximize the probability of effectiveness against unknown viral threats. Currently, first generation vaccines are
being deployed to combat SARS-CoV-2, but their effectiveness against emergent SARS-CoV-2 variants and,
importantly, against other potential zoonotic coronaviruses is unknown. This program will focus on neutralizing
antibodies as a demonstrated and key component of protective immune responses. The Program will improve
preparedness against coronaviruses, employing a progressive multistep approach to increase the breadth of
vaccine protection. A key component of the research will be to comprehend how neutralizing antibody
responses, elicited in humans following natural infection or vaccination, target the SARS-CoV-2 envelope
spike and how antibody evolution leads to increased potency and breadth. The identification and
characterization of epitopes targeted by SARS-CoV-2 neutralizing antibodies, using multiple approaches, will
guide the design of immunogens that aim to elicit neutralizing antibodies targeting as diverse a spectrum of
coronaviruses as possible. Several immunogens and delivery strategies will be tested in mice and hamsters
that will be challenged with authentic SARS-CoV-2 or a panoply of newly developed challenge models
incorporating divergent coronavirus spike proteins. Antibodies elicited in these animals will be analyzed and
compared with those found in SARS-CoV-2 immunized humans and immunogens progressively refined and
down-selected with the goal of performing vaccine-challenge experiments in nonhuman primates with the most
promising candidates. The expertise of each participating team is highly complementary and the program will
capitalize and build on the already existing scientific synergy to ensure the efficient and timely completion of
the goals.
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><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Animal Experiments><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><Antigenic Determinants><Antigens><Assay><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><Blood Plasma><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 S protein><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 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19><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><CV-19><CV19><Cessation of life><Clinical Treatment Moab><Cloning><CoV S protein><CoV emergence><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><Cricetinae><Data><Death><Effectiveness><Ensure><Epidemic><Epitope Mapping><Epitopes><Event><Evolution><Generations><Goals><Hamsters><Hamsters Mammals><Health><Hu-mABs><Human><Immune response><Immunity><Immunize><Immunological response><Individual><Infection><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Monoclonal Antibodies><Murine><Mus><Nature><Patients><Plasma><Plasma Serum><Population><Preparedness><Probability><Readiness><Reagent><Recurrence><Recurrent><Reporting><Research><Reticuloendothelial System, Serum, Plasma><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><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-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><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><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 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><Speed><Structure><T cell response><Techniques><Testing><Time><Vaccination><Vaccines><Viral><Virus><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><animal coronavirus><animal experiment><cohort><combat><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><corona virus emergence><coronavirus S protein><coronavirus disease 2019><coronavirus disease 2019 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 spike glycoprotein><coronavirus disease 2019 spike protein><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><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus emergence><coronavirus infectious disease-19><coronavirus of pandemic concern><coronavirus of pandemic potential><coronavirus spike glycoprotein><coronavirus with pandemic potential><design><designing><develop a vaccine><develop therapy><develop vaccines><development of a vaccine><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><experience><experiment><experimental animal><experimental animals><experimental research><experimental study><experiments><hCoV19><host response><humAbs><human disease><human mAbs><human monoclonal antibodies><human monoclonals><immune system response><immunogen><immunoresponse><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><intervention development><mAbs><model of animal><monoclonal Abs><mutant><nCoV><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neutralizing antibody><new CoV><new corona virus><new coronavirus><next generation><non-human primate><nonhuman primate><novel><novel CoV><novel corona virus><novel coronavirus><pandemic><pandemic concern><pandemic coronavirus><pandemic disease><pandemic potential><pandemic risk><pandemic threat><pandemic threat coronavirus><prevent><preventing><programs><recruit><response><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><therapy development><treatment development><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 development><vaccine for novel coronavirus><viral epidemic><volunteer><weapons><zoonotic CoV><zoonotic coronavirus>