# Novel B. Pertussis vaccines that elicit mucosal immunity

> **NIH NIH R56** · OHIO STATE UNIVERSITY · 2024 · $657,506

## Abstract

Project Abstract
Despite high global vaccination rates, pertussis caused by the gram-negative bacterial pathogen Bordetella
pertussis (Bp) is re-emerging in vaccinated individuals. This is correlated with the switch in the 1990s from whole
cell (wPV) to acellular vaccines (aPV). wPV elicit TH1/TH17 polarized immune responses and clear Bp from the
entire respiratory tract. In contrast, aPV elicit TH2 polarized immunity and do not prevent nasal colonization.
Thus, aPV immunized individuals serve as reservoirs for transmission to vulnerable populations.
While the importance of CD4+ T cells for long-term protection against Bp infection is established, the antigens
recognized by the T cells remain undefined. Using high dimensional mass spectrometry and functional T cell
assays we identified several new antigens from Bp that generate tissue-resident memory T cell responses in
mice and are recognized by CD4+ T cells from wPV immunized people. In this application we will test the efficacy
of a subunit vaccine containing these antigens and the TH1/TH17 polarizing adjuvants Bordetella Colonization
Factor A (BcfA) and double mutant heat-labile toxin (dmLT). These adjuvants activate immune responses through
different mechanisms and elicit mucosal immunity. We hypothesize that these vaccines will elicit long-lived
TH1/TH17 tissue-resident T cell responses in the nose and lungs, and clear Bp from the nose, thereby reducing
the likelihood of Bp transmission by vaccinated individuals.
Specific Aim 1: To test the ability of an intranasal subunit booster vaccine containing new T cell
recognized antigens to reduce Bp colonization in aPV primed adult mice.
We will test an intranasal (i.n) booster vaccine containing the TH1/TH17 polarizing adjuvant BcfA, admixed with
detoxified pertussis toxin and three new T cell antigens, in mice previously immunized intramuscularly (i.m) with
an approved aPV. The systemic and mucosal T cell and antibody responses will be quantified, along with the
phagocytes recruited to the respiratory tract, and the Bp bacterial load in the nose and lungs.
Specific Aim 2: To test the immunogenicity and protective efficacy in infant mice of a subunit vaccine
delivered by a heterologous immunization regimen.
We will test the novel T cell antigens combined with the adjuvants dmLT and BcfA, separately and together.
Vaccines containing dmLT will be tested by the i.d route and vaccines containing BcfA will be tested by the i.d or
i.n route. Immune responses, bacterial load and the longevity of protection will be determined.
IMPACT: There is a critical need for next generation pertussis vaccines that elicit mucosal immunity and prevent
nasal colonization. The proposed experiments will test a vaccine formulation containing novel MHC Class II
presented antigens that will provide sustained protection against Bp infection as a booster and as a pediatric
vaccine. These foundational studies will lead to a safe and effective next generation pertussis vaccine ...

## Key facts

- **NIH application ID:** 11131535
- **Project number:** 1R56AI183683-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** RAJENDAR K DEORA
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $657,506
- **Award type:** 1
- **Project period:** 2024-08-06 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11131535

## Citation

> US National Institutes of Health, RePORTER application 11131535, Novel B. Pertussis vaccines that elicit mucosal immunity (1R56AI183683-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11131535. Licensed CC0.

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