# Development of Viral Vaccines against Sarbecoviruses and Merbecoviruses

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2022 · $2,161,141

## Abstract

Project Summary
Over the past twenty years, six coronaviruses (CoV) have emerged or expanded their geographic range. The
emergent human CoVs with the greatest global impact (SARS-CoV-1, SARS-CoV-2, and MERS-CoV) belong to
the Sarbecovirus and Merbecovirus subgenera within the Betacoronavirus genus of the Coronaviridae family.
Many zoonotic high-risk Sarbecoviruses and Merbecoviruses are poised for human emergence events because
they can bind human ACE2 and DPP4 entry receptors and infect human cells in culture. Given the historical
outbreaks of CoVs, coupled with the recent emergence of SARS-CoV-2 and its destabilizing consequence on
global health and economy, there is an urgent need to develop vaccines capable of broad protection against
existing and future Sarbecoviruses and Merbecoviruses. Thus, the overarching goal of this P01 proposal is to
generate viral-vectored vaccines that induce broad cross-protective humoral and cellular immunity to
Sarbecoviruses and Merbecoviruses with pandemic potential, especially those viruses at high risk for zoonotic
emergence into human populations. Project 3 will use antigen and epitope designs from Projects 1 and 2 to
create vaccine platforms that generate cross-reactive immune responses against Sarbecoviruses and
Merbecoviruses with pandemic potential. We will use several spike (S), RBD, and non-structural protein antigens
that can be administered as part of a polyvalent formulation to induce broad B and T cell immunity. Project 3
will perform parallel and iterative engineering of an intranasally delivered chimpanzee adenoviral vectored virus
(ChAd) and an intramuscularly delivered live-attenuated vesicular-stomatitis virus (VSV) displaying or producing
optimized antigens. Antigens and vaccines that show immune responses of the highest magnitude and greatest
cross-reactivity (determined with Core A) will be tested in in naïve, virus-immune, and mRNA vaccinated mice
to determine how pre-existing immunity to SARS-CoV-2 impacts the immunogenicity of our more broadly
targeting CoV vaccines. Vaccines showing optimal B and T cell immunogenicity (breadth, magnitude, and
function) will be prioritized for mouse and hamster challenge studies in Core B with multiple Sarbecoviruses and
Merbecoviruses. Our proposal is a proof-of-principle for product development. We envision generating at least
one vaccine that induces broad-spectrum immunity to multiple CoV of concern.

## Key facts

- **NIH application ID:** 10420516
- **Project number:** 1P01AI168347-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael S Diamond
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,161,141
- **Award type:** 1
- **Project period:** 2022-09-02 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10420516

## Citation

> US National Institutes of Health, RePORTER application 10420516, Development of Viral Vaccines against Sarbecoviruses and Merbecoviruses (1P01AI168347-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10420516. Licensed CC0.

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