# Project 3: Mechanistic studies and comparisons of vaccines in preclinical models

> **NIH NIH P01** · UNIVERSITY OF WASHINGTON · 2022 · $1,377,304

## Abstract

PROJECT SUMMARY– PROJECT 3: Mechanistic studies and comparisons of vaccines in preclinical
models
The two primary goals of the Project are to: (i) define the immunological parameters (i.e., CD4+ T cell help;
innate immune response) that regulate the breadth of the antibody response in mechanistic studies in mice,
and (ii) evaluate pan-sarbecovirus and pan-betacoronavirus vaccine candidates aimed at inducing broadly
protective immune responses in nonhuman primates (NHPs) (with Core D, Nonhuman Primates, Villinger).
In Aim 1, we will determine the mechanisms by which the innate immune system and T follicular cells regulate
the breadth of antibody responses induced by broadly protective coronavirus vaccines designed in Project 2
(King). We will perform mechanistic studies in mice to determine the impact of CD4+ T cell help and specific
DC subsets in regulating the breadth of vaccine-elicited Ab responses. This will yield insights about critical
immunological parameters that determine antibody breadth and, looking ahead, provide a rational basis for the
development of adjuvants that stimulate broad Ab responses. In Aim 2 we will conduct two studies in NHPs to
evaluate pan-sarbecovirus and pan-betacoronavirus vaccine candidates from Project 2 and select lead
candidates for further preclinical and clinical development. These studies will use clinically relevant adjuvants
to ensure optimal translation to humans. We will assess the magnitude, breadth and durability of nAb
responses induced by immunization with nanoparticle immunogens formulated with AS03 and 3M-052/alum,
both of which have demonstrated superior adjuvant effects in terms of their capacity to promote
high-magnitude and durable neutralizing antibody responses in NHPs. We will thus directly compare AS03 with
3M-052/alum for their capacity to enhance the breadth of nAb responses. We will work with Project 1
(Veesler) and Cores B (Virology, Baric), C (Viral Evolution, Bloom) and D to evaluate the immunogenicity
and protective breadth of the responses elicited by each nanoparticle vaccine candidate and define the epitope
specificities of cross-reactive responses. We will characterize the dynamics of the antigen-specific B cell
response, assess plasmablast and plasma cell frequencies, and sort antigen-specific single B cells and isolate
monoclonal antibodies from immunized NHPs. These mAbs will be produced by Core A (Protein Sciences,
King) and analyzed in Project 1 and Cores B and C for their binding and neutralizing breadth, epitope
specificity, and resistance to escape mutations.

## Key facts

- **NIH application ID:** 10425032
- **Project number:** 1P01AI167966-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** BALI PULENDRAN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,377,304
- **Award type:** 1
- **Project period:** 2022-09-02 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425032

## Citation

> US National Institutes of Health, RePORTER application 10425032, Project 3: Mechanistic studies and comparisons of vaccines in preclinical models (1P01AI167966-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10425032. Licensed CC0.

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