# Identification of novel immunogenic proteins from Bordetella pertussis

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $764,867

## Abstract

PROJECT SUMMARY
Despite high vaccination coverage, pertussis outbreaks caused by the gram-negative obligate human pathogen
Bordetella pertussis (Bp) are observed in many countries. Pertussis resurgence correlates with the switch in the
1990s from whole cell vaccines (wPV) which elicit long-lived Th1/17 immune responses, to acellular vaccines
(aPV) which elicit Th1/2 skewed immune responses. Furthermore, aPV do not prevent nasal colonization or
transmission of Bp. Current aPV are comprised of 1-5 bacterial proteins that were selected for their roles in
pathogenesis and ability to elicit antibodies. In contrast, wPV present an undefined large number of antigens.
The combination of limited antigenic diversity and Th2 skewed immune profile is a likely explanation for the
incomplete protection provided by aPV. Recent studies including that from our laboratory also show that
circulating Bp strains (CBp) from globally diverse countries have absent/reduced expression of current aPV
antigens, suggesting that aPV may be significantly less effective against CBp strains. There is increasing
recognition that CD4+ T cell responses are critical for long-lived protective immune responses that clear the
entire respiratory tract. However, it is not clear that current aPV antigens are optimal CD4+ T cell targets. We
will use state-of-the-art mass spectrometry, bioinformatics, and phenotypic and functional assays to identify
proteins expressed by CBp that are processed and presented on Class II histocompatibility antigens of humans
and mice, and that stimulate CD4+ T cell responses. This foundational data set will be coupled with a prime-pull
vaccination strategy and a Th1/17 skewing adjuvant developed in our laboratory, to determine the
immunogenicity and protective efficacy of newly defined antigens to create a next-gen aPV.
 Specific Aim 1: Define the set of naturally derived Bp peptides presented on MHC II and
recognized by CD4+ T cells. We will identify the Bp antigens from circulating Bp strains (CBp) that are
expressed on human and murine Class II, and use proliferation and flow cytometry assays to determine which
antigens are recognized by CD4+ T cells of wPV-immunized individuals and convalescent mice.
 Specific Aim 2: To test the immunogenicity and protective efficacy of novel antigens against
circulating Bp strains and their role in pathogenesis. We will test the immunogenicity and protective efficacy
of the novel proteins using a murine model of Bp infection. We will create deletion mutants of the novel proteins
in CBp to determine their role in pathogenesis and colonization of the respiratory tract.
IMPACT: Our integrated approach to identify, test, and leverage novel Bp antigens will permit the rational design
of next-gen aPVs that elicit long-lasting protection in the respiratory tract, prevent nasopharyngeal carriage and
thereby reduce the spread of the disease pertussis.

## Key facts

- **NIH application ID:** 10425440
- **Project number:** 5R01AI153829-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** RAJENDAR K DEORA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $764,867
- **Award type:** 5
- **Project period:** 2021-06-09 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425440

## Citation

> US National Institutes of Health, RePORTER application 10425440, Identification of novel immunogenic proteins from Bordetella pertussis (5R01AI153829-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10425440. Licensed CC0.

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