# Structural Characterization of Coronavirus Antibodies Raised by Infection and Vaccination

> **NIH NIH P01** · ROCKEFELLER UNIVERSITY · 2022 · $1,507,637

## Abstract

Project 3: Summary/Abstract
SARS-CoV-2, a newly-emergent betacoronavirus in the sarbecovirus genus, resulted in a global pandemic in
2020, infecting millions and causing COVID-19 disease. Two other zoonotic betacoronaviruses, SARS-CoV (a
sarbecovirus) and MERS-CoV (a merbecovirus), also resulted in outbreaks within the last 20 years. SARS-like
viruses circulate in bats and serological surveillance of people living near caves where bats carry diverse
coronaviruses demonstrate direct transmission of SARS-like viruses with pandemic potential, suggesting a pan-
coronavirus vaccine is needed. In Project 3, the Bjorkman lab will use structural biology and biochemical
approaches to understand the neutralization mechanisms of antibodies (Abs) elicited in humans by SARS-CoV-
2 infection or vaccination and in experimental animals by immunization. In Aim 1, using 3D structures of Ab Fabs
bound to coronavirus spike (S) trimers, we will derive the structural correlates of neutralization/binding for
monoclonal Abs (mAbs) and polyclonal plasmas isolated in Project 1 by Dr. Nussenzweig from (i) humans
infected by SARS-CoV-2 after ~1 month, (ii) matured human Abs isolated ½ - 2 years after infection, (iii) humans
vaccinated against SARS-CoV-2 with the Moderna vaccine, and (iv) animals immunized with vaccine candidates
developed in Project 2 by Drs. Bieniasz and Hatziioannou or developed in this project's Aim 2 in the Bjorkman
laboratory. Aim 2 of this project will follow up on our lab's evaluations of the potential for cross-reactive antibody
responses to sarbecoviruses, for which we made homotypic nanoparticles presenting the receptor-binding
domain (RBD) of only SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal
betacoronaviruses (mosaic nanoparticles; 4-8 distinct RBDs). By combining results of functional analyses of Ab
neutralization derived from pseudotyped and authentic virus neutralization assays in collaboration with Dr. Rice
with structural analyses of Abs isolated from RBD-nanoparticle–injected mice, we will refine our nanoparticle
vaccine candidate(s) to increase their potential to protect against sarbecoviruses. Furthermore, we will develop
additional vaccine candidates against merbecoviruses and/or alphacoronaviruses that will be evaluated along
with the best pan-sarbecovirus vaccine in animal models of protection by Dr. Rice and/or our NIH collaborator,
Dr. Vincent Munster. This highly-integrated project has the potential to contribute to creation of vaccine(s) that
could avert future global pandemics.

## Key facts

- **NIH application ID:** 10327994
- **Project number:** 1P01AI165075-01
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Pamela J Bjorkman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,507,637
- **Award type:** 1
- **Project period:** 2022-01-03 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327994

## Citation

> US National Institutes of Health, RePORTER application 10327994, Structural Characterization of Coronavirus Antibodies Raised by Infection and Vaccination (1P01AI165075-01). Retrieved via AI Analytics 2026-06-07 from https://api.ai-analytics.org/grant/nih/10327994. Licensed CC0.

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