Antibody Core

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Principal Investigator: Ali Hassan Ellebedy
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2023
Award: $208,535
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. A multidisciplinary team of scientists from five institutions who have an outstanding track record of
working collaboratively will conduct the proposed studies. The Research Projects will collaborate with each
other and with the Antibody and Animal Model Cores, coordinated by the Administrative Core. 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.

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