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Principal Investigator: Charles M Rice
Organization: ROCKEFELLER UNIVERSITY
Fiscal Year: 2023
Award: $983,100
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary – BSL3 Virology and Animal Models Core
The COVID-19 pandemic has disrupted all aspects of society across the globe. The overarching theme of this
P01 proposal is to study immune responses to infection with SARS-CoV-2 and their reactivity against other
coronaviruses (CoVs) such that immunization strategies resulting in broad neutralizing activity can be tested with
the ultimate goal of developing a vaccine that will provide protection against likely future emerging CoVs. The
goals of the BSL3 Virology and Animal Models Core (Charles Rice/Margaret MacDonald) are to generate
reagents and develop and perform assays in support of the objectives of three Research Projects, headed by
Drs. Michel Nussenzweig and Marina Caskey (Project 1), Drs. Paul Bieniasz and Theodora Hatziioannou
(Project 2) and Dr. Pamela Bjorkman (Project 3). Together the three Projects, the Virology and Animal Models
Core and the Administrative Core aim to accomplish the Program's goal of defining the breadth of serological
immunity in SARS-CoV-2 infected or vaccinated individuals, to define any conserved epitopes targeted by
neutralizing antibodies, to investigate mechanisms of neutralization using structural and functional approaches,
and to test in small animal models immunogens designed to elicit antibodies with maximum neutralization
breadth. To meet the program goals, molecular virology, cell culture and animal model approaches will be taken
by the BSL3 Virology and Animal Models Core in four Aims to 1) develop CoV working stocks for in vitro and
in vivo use (Projects 1, 2 and 3), 2) develop facile systems for testing the neutralization activity of sera and cloned
antibodies using trans-packaged replicons (TPRs) bearing the spike proteins of a broad range of CoVs, including
those of potential pandemic concern (Projects 2 and 3), 3) conduct in vitro neutralization assays against SARS-
CoV-2 and other CoVs or TPRs using the best candidate sera and cloned antibodies from humans and animal
models from all three Projects and 4) perform immunization and protection experiments in small animal models
to test the efficacy of candidate monoclonal antibodies and vaccination strategies. Overall, the work will
contribute significantly to the development of pan-CoV vaccine candidates that can be used to mitigate the threat
of future CoV pandemics.
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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-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 pandemic><Severe acute respiratory syndrome related corona virus 2><Societies><Syrian Hamsters><System><Testing><Transgenic Organisms><Vaccinated><Vaccinee><Virus><Work><Wuhan coronavirus><angiotensin converting enzyme 2><angiotensin converting enzyme II><antibody neutralization test><cell 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individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination strategy><vaccine candidate><vaccine development><virology>