# Combined adjuvant approaches for enhancement of SARS-CoV-2 vaccine efficacy

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $744,600

## Abstract

PROJECT SUMMARY/ABSTRACT
The high morbidity and mortality associated with Covid-19 continues to underscore the importance of effective
vaccines against SARS-CoV-2. While a few promising candidates have received EUAs, the emergence of more
transmissible variants which have impacted vaccine efficacy highlight the fact that several challenges remain. A
successful vaccine must: 1. induce robust long-lasting protection when natural infection with coronaviruses
generally leads to relatively short-lived immunity, 2. impart broad immunity as viral mutations accumulate, 3.
provide potent immunity in the elderly, and 4. be safe in light of enhanced disease observed with past coronavirus
vaccines. To address these challenges, this proposal aims to develop a safe, effective, and rapidly translatable
adjuvant system for SARS-CoV-2 vaccines using a rationally designed combination adjuvant to target an array
of key innate receptor pathways involved in antiviral immunity. Adjuvants are powerful tools for promoting fast,
durable and qualitative responses most effective for a particular pathogen, especially in immune-challenged
individuals. Natural viral infection stimulates strong immune responses through activation of Toll-, RIG-I-, and
NOD-like receptors (TLRs, RLRs, NLRs). As induction of appropriate innate responses is crucial for long-lasting
adaptive immunity and for shaping the correct types of immune responses, we will test the hypothesis that using
a combination of agonists that integrate these pathways will lead to improved humoral and cellular responses
towards SARS-CoV-2. To achieve this, we will combine a nanoemulsion-based adjuvant (NE) that activates
TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). We have demonstrated that simultaneous activation of
TLRs, RIG-I, and NLRP3 with NE/IVT DI induces a synergistic immune response with magnified TH1-biased
cellular immunity. Guided by strong preliminary data demonstrating the effectiveness of this combined adjuvant
approach for improving influenza virus vaccination, and our initial studies with SARS-CoV-2 antigens, we will
develop this adjuvant for use in a SARS-CoV-2 vaccine in two specific aims. In Aim 1, we will profile the immune
responses elicited by NE/IVT DI with multiple SARS-CoV-2 antigens through parenteral and mucosal routes to
optimize formulations and vaccination routes. In Aim 2, we will determine the protective efficacy and safety of
the optimized lead vaccine platforms in challenge models of SARS-CoV-2 and define key correlates of protection.
Increasing data suggests that SARS-CoV-2 elicits a weak innate response, with poor activation of critical antiviral
pathways, which likely contributes to the large variability in magnitude and durability of immune responses in
recovered patients. With this targeted approach, we expect to drive more robust and durable immunity while
avoiding immune responses promoting vaccine related pathology. The NE adjuvant and several RIG-I agonists
have demo...

## Key facts

- **NIH application ID:** 10361957
- **Project number:** 1R01AI160706-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Michael Schotsaert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $744,600
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361957

## Citation

> US National Institutes of Health, RePORTER application 10361957, Combined adjuvant approaches for enhancement of SARS-CoV-2 vaccine efficacy (1R01AI160706-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10361957. Licensed CC0.

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