# Integrative Immunogen Design and Testing

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $2,628,877

## Abstract

Project 3 Summary
Coronaviruses will likely remain a persistent threat to human health. However, whether the next significant
disease outbreak will be caused by a known coronavirus, another novel coronavirus, or continued surges from
variant(s) of SARS-CoV-2 is unknown. The goal of this project is to develop novel, improved immunogens to
elicit broader anti-coronavirus immunity, to structurally evaluate resulting pan-coronavirus or broad-coronavirus
antibodies, and to evaluate efficacy of broad coronavirus vaccines in animal models. We will begin with novel
third-generation spikes that better remain in a pre-fusion quaternary assemblies relative to earlier versions of
spike that have been described in the literature. These novel spike proteins, termed “VFLIP”, retain a trimeric
conformation even in the absence of exogenous trimerization motifs, are resistant to thermal denaturation,
feature glycan structures that better reflect those on authentic virions and offer receptor-binding domain positions
and conformation that also better reflect those on native virions. These molecules further feature slower “off”
rates for a wide panel of anti-coronavirus antibodies. In this program, we will develop novel immunogens from
these improved spikes alone and as part of innovative multimeric vaccine particles. Our collaborating projects
will evaluate these immunogens for their ability to elicit broad B- and T-cell immune responses. We will then
evaluate the efficacy of the best candidate immunogens in mouse and hamster models of infection using multiple
relevant coronaviruses. This project represents the beginning and end of the collaborative, iterative circle of
immunogen design and evaluation. Cycles of in-depth evaluation and iteration will shepherd vaccine efforts for
broad protection against the growing threat posed by coronaviruses.

## Key facts

- **NIH application ID:** 10328121
- **Project number:** 1P01AI165072-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Erica Ollmann Saphire
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,628,877
- **Award type:** 1
- **Project period:** 2021-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328121

## Citation

> US National Institutes of Health, RePORTER application 10328121, Integrative Immunogen Design and Testing (1P01AI165072-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328121. Licensed CC0.

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