# Engineering Immunity for Broad Protection Against Betacoronaviruses

> **NIH NIH K08** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $199,584

## Abstract

Abstract
In the past decade three highly virulent human betacoronaviruses have emerged, including SARS-CoV-2 which
has caused a devastating pandemic and is responsible for the deaths of over 6 million people worldwide. Current
vaccines and monoclonal antibody (mAb) treatments for SARS-CoV-2 are susceptible to mutations in the virus
which can lead to decreased efficacy of these therapies. Two other highly pathogenic human betacoronaviruses,
SARS-CoV and MERS-CoV, have no approved vaccines or therapeutics. There is an urgent need for broadly
acting antibodies and vaccines which can protect against new variants of SARS-CoV-2 or future emerging
human betacoronaviruses. Our current vaccines and mAbs for SARS-CoV-2 target the viral spike protein. The
spike (S) is necessary and sufficient to mediate entry of the virus into host cells. S is comprised of two subunits.
S1 is the receptor binding subunit and a major target of antibodies produced by current vaccines and mAb
therapies. S2 is the membrane fusion subunit and is highly conserved among betacoronaviruses. Little is known
about S2 targeting antibodies and their potential use in protecting against betacoronavirus infections. In this
project we will identify and design broadly acting S2 antibodies as well as investigate Fc-effector functions of
these antibodies. A multipronged approach using neutralization assays, in vitro Fc-effector function assays and
systems serology will evaluate the functional properties of S2 antibodies from mice immunized with S2
immunogens. Using a panel of replication competent vesicular stomatitis virus (rVSV) pseudotype viruses
expressing the spike protein from a wide range of betacoronaviruses (rVSV-CoVs) we will be able to identify
antibodies that are broadly acting. Finally, by using what we learn in our analysis of endogenously produced S2
antibodies we will design bispecific S2 targeting antibodies to develop novel therapeutics broadly targeting
betacoronaviruses. This project will significantly add to our knowledge of the role S2 antibodies play in infection
with betacoronaviruses and how these antibodies can be utilized for future pandemic preparedness.

## Key facts

- **NIH application ID:** 10984676
- **Project number:** 1K08AI180364-01A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Emily Happy Miller
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $199,584
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984676

## Citation

> US National Institutes of Health, RePORTER application 10984676, Engineering Immunity for Broad Protection Against Betacoronaviruses (1K08AI180364-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10984676. Licensed CC0.

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