# Mucosal subunit vaccines against SARS CoV-2

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $769,833

## Abstract

With the emergence of SARS-CoV-2 variants with mutations in the Spike protein, there remains an urgent need
for vaccines that are both effective against variants and that generate long-lived mucosal immunity. Generation
of durable cell-mediated and humoral immunity is critical for optimal naturally occurring and vaccine-induced
protection against respiratory pathogens, including SARS-CoV-2, and includes IFN-γ and IL-17 producing tissue-
resident memory T (TRM) cells, T follicular helper (TFH) cells, germinal center (GC) and memory B cells, that
contribute to the production of pathogen-specific neutralizing antibodies.
Most currently approved vaccines are adjuvanted with alum, which is a strong adjuvant that elicits TH2 skewed
cellular and humoral responses, associated with short-lived immunity to intracellular respiratory pathogens.
Experimental adjuvants that generate TH1 and TH17 driven systemic and mucosal responses, provide effective
and long-lived protection against infection.
Bordetella Colonization Factor A (BcfA) is an adjuvant that elicits strong TH1 and TH17 responses and has the
unique ability to attenuate the detrimental TH2 responses primed by alum. Polyfunctional IL-21 and IFN-γ (TFH1
cells) or IL-21 and IL-17 (TFH17 cells) cells are important for generation of effective antibodies against viral
respiratory pathogens. The TH1/TH17 skewing properties of BcfA may promote the differentiation and function of
these specialized TFH cell populations.
Mucosal vaccination is a more effective means of generating tissue-resident memory that is not generated by
parenterally administered alum-adjuvanted vaccines. A prime-pull regimen (systemic priming and intranasal
booster) generates mucosal responses to vaccines containing TH1/TH17 skewing adjuvants and provides
superior protection. We will test the overarching hypothesis that a BcfA/alum-adjuvanted subunit SARS
CoV-2 vaccine containing S, M and N proteins, delivered via a heterologous prime-pull immunization regimen
will reduce SARS-CoV-2 infection of the mouse respiratory tract and elicit long-lived systemic and
mucosal TH1/TH17 driven immune responses.

## Key facts

- **NIH application ID:** 10999830
- **Project number:** 1R01AI181270-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** RAJENDAR K DEORA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $769,833
- **Award type:** 1
- **Project period:** 2024-06-05 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999830

## Citation

> US National Institutes of Health, RePORTER application 10999830, Mucosal subunit vaccines against SARS CoV-2 (1R01AI181270-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10999830. Licensed CC0.

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