# Design and evaluation of pan-CoV vaccines

> **NIH NIH P01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $4,242,156

## Abstract

SUMMARY
 As part of the Pan-Coronavirus Vaccine (PanCoVac) Consortium, the goal of Research Project 1 (RP1) is
the ‘Design and evaluation of pan-CoV vaccines’. A comprehensive characterization of the B and T cell
responses to vaccination will be carried out by Research Project 2 (RP2, ‘Immunological responses to pan-CoV
vaccines. In Aim 1 of RP1 (‘Focusing immune responses towards the stem of the spike protein’), several
strategies will be tested to increase the levels of antibodies directed at the conserved, immune-subdominant
epitopes in the stem of the SARS-CoV-2 spike protein (to major viral antigen), while avoiding strong antibody
responses directed at immunodominant epitopes in the head of the spike protein. These strategies include
chimeric spikes composed of SARS-CoV-2 immune-subdominant stem epitopes and immunodominant head
epitopes of unencountered coronaviruses, ‘outdiluting’ antibody responses to the immunodominant epitopes by
using cocktails of spike proteins with multiple mutations in key amino acid positions, glycan-shielding of
immunodominant head epitopes, ‘inverted antigens’ in which the spike protein will be presented to the immune
system in an inverted orientation (and thus become more accessible), and ‘headless’ spike proteins lacking
portions of the immunodominant head epitopes. Some of these approaches may be tested in combination, and
may be tested with sequence-optimized stem epitopes based on ancestral reconstruction (a computational
approach to deduce the most likely common progenitor sequence). In Aim 2 (‘Eliciting broadly reactive
immune responses to the head of the spike protein’), strategies will be tested to direct the immune responses
away from the most sequence-diverse epitopes and towards more conserved epitopes in the head. In addition,
conserved heard epitopes will be sequenced-optimized to be recognized by cross-protective antibodies. These
modifications will be introduced into diverse spike proteins, and vaccine cocktails of diverse, mutant spike
proteins will then be tested for their immunogenicity and protective efficacy. All antigens in Aims 1 and 2 will be
designed in collaboration with a structural biologist, and for selected antigens and/or antigen/antibody complexes,
X-ray crystallography and Cryo-EM will be carried out. In Aim 3 (‘Immunogenicity and protective efficacy of
broadly reactive antigens’), the novel vaccinates will be tested in mice for their immunogenicity; samples from
vaccinated mice will be provided to RP2 for B and T cell analysis. Selected vaccine candidates (those with
broader immune responses) will next be tested in mice and Syrian hamsters for their ability to provide protection
against different coronaviruses. For candidate vaccines that provide broad protection (compared to controls), we
will also assess the durability of immune responses, and the effect of vaccination on virus transmissibility.
Moreover, these vaccinate candidates will be tested in an mRNA lipid nanoparticle va...

## Key facts

- **NIH application ID:** 10327848
- **Project number:** 1P01AI165077-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** YOSHIHIRO KAWAOKA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $4,242,156
- **Award type:** 1
- **Project period:** 2021-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327848

## Citation

> US National Institutes of Health, RePORTER application 10327848, Design and evaluation of pan-CoV vaccines (1P01AI165077-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327848. Licensed CC0.

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