# Project 2: Structure-based antigen and nanoparticle vaccine design

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2022 · $792,967

## Abstract

PROJECT SUMMARY – PROJECT 2: Structure-based antigen and nanoparticle vaccine design
Project 2 is focused on the design, production, and characterization of novel stabilized antigens and broadly
protective nanoparticle vaccines. In Aim 1, we will establish automated computational pipelines that identify
sets of novel prefusion-stabilizing mutations in the spike proteins of various sarbecovirus, merbecovirus, and
embecovirus strains we will use in our broadly protective vaccines. Our recent work has also demonstrated the
utility of using deep mutational scanning data to guide the identification of stabilizing mutations in isolated
SARS-CoV-2 receptor-binding domains (RBD). The computational pipelines we develop will extend this
method to the design of additional stabilized RBD antigens across all four known clades of sarbecoviruses for
use in pan-sarbecovirus vaccines. In Aim 2, we will computationally design novel self-assembling protein
nanoparticle scaffolds that present prefusion spike trimers in arrays specifically designed to allow
unconstrained B cell receptor/antibody access to broadly conserved epitopes. We hypothesize that these
scaffolds will elicit antibody responses with superior protective breadth, particularly when used as the basis for
mosaic nanoparticle immunogens. We will experimentally validate several novel nanoparticles and prototype
their functional performance as monovalent nanoparticle immunogens in immunization and challenge studies
in mice to identify the scaffolds that best focus the humoral immune response on conserved epitopes. In Aim 3
we will build on our recent work demonstrating the elicitation of broadly protective immune responses against
influenza by generating multivalent nanoparticle vaccines displaying multiple coronavirus RBDs or prefusion
spikes. We will take a hierarchical, phylogeny-driven approach. We will focus at first on developing a
pan-sarbecovirus vaccine, which will display multiple RBD or prefusion spike antigens. We will then generate
broadly protective merbecovirus and embecovirus vaccines displaying multiple prefusion spikes. Finally, we will
define the optimal composition of a pan-betacoronavirus nanoparticle vaccine. We will work closely with the
other groups in our Program to identify lead pan-sarbecovirus and pan-betacoronavirus vaccine candidates for
further preclinical and clinical development at the end of Years 2 and 5 of our Program, respectively.

## Key facts

- **NIH application ID:** 10425031
- **Project number:** 1P01AI167966-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Neil King
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $792,967
- **Award type:** 1
- **Project period:** 2022-09-02 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425031

## Citation

> US National Institutes of Health, RePORTER application 10425031, Project 2: Structure-based antigen and nanoparticle vaccine design (1P01AI167966-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10425031. Licensed CC0.

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