Programming Long-lasting Immunity to Coronaviruses (PLUTO)

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Ali Hassan Ellebedy
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2023
Award: $2,506,857
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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