# Understanding antibody responses and defining correlates of protection for endemic and pandemic coronavirus strains

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $1,037,822

## Abstract

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.

## Key facts

- **NIH application ID:** 10910984
- **Project number:** 5P01AI172531-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Viviana A Simon
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,037,822
- **Award type:** 5
- **Project period:** 2023-08-21 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910984

## Citation

> US National Institutes of Health, RePORTER application 10910984, Understanding antibody responses and defining correlates of protection for endemic and pandemic coronavirus strains (5P01AI172531-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10910984. Licensed CC0.

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