# Enhanced immunogenicity and protection study of lipid modified protein vaccine candidates of Nontypeable Haemophilus influenzae

> **NIH NIH R21** · ROCHESTER GENERAL HOSPITAL (NY) · 2020 · $240,000

## Abstract

Abstract:
In the conjugate vaccine era, Nontypeable Haemophilus influenzae (NTHi) has become the
leading cause of acute otitis media (AOM), recurrent AOM, acute sinusitis and conjunctivitis in
children and adults and acute exacerbations of chronic obstructive pulmonary disease (COPD) in
adults. There is need to develop a vaccine against NTHi. Various vaccine candidates have been
explored but still there is need for enhancement of antibody and Th17 immunity response for NTHi
vaccines that will help prevent nasopharyngeal colonization and infection. In this project we will
compare immunogenicity of recombinant proteins P6 and OMP26 and their fusion constructs in
their lipidated and non-lipidated form in a mouse coinfection model of NTHi-AOM, we developed.
Two proteins were selected based on their different function and considering P6 is naturally
lipidated and native OMP26 is not but is known to induce Th17 immunity. We will test our
hypothesis that lipidated protein antigens elicit higher blood and mucosal antibody levels as well
as Th17 immune response (via toll-like receptor 2 activation) than non lipidated proteins. Lipidated
protein antigens will elicit greater reduction in ear and nasal bacterial loads compared to
nonlipidated antigens against NTHi. The contribution and mechanism of antibody mediated and
TH17-mediated immunity in protection against NTHi will be compared in infant and adult mice as
well as in TLR2-knock out mice using lipidated, nonlipidated and fusion constructs of vaccine
candidates P6 and OMP26. We will test whether lipidated proteins produce a more robust IL-17A
response from memory Th17 cells in the nasopharynx that helps traffic neutrophils and show
enhanced NTHi clearance compared to nonlipidated protein antigens. Overall, the proposed
studies will significantly advance our understanding of enhanced immunogenicity of recombinant
proteins and molecular mechanisms underlying the lipidation regulation of TLR-2 dependent
Th17- immunity in NTHi vaccine development.

## Key facts

- **NIH application ID:** 10042550
- **Project number:** 1R21AI153936-01
- **Recipient organization:** ROCHESTER GENERAL HOSPITAL (NY)
- **Principal Investigator:** Ravinder Kaur
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,000
- **Award type:** 1
- **Project period:** 2020-08-21 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042550

## Citation

> US National Institutes of Health, RePORTER application 10042550, Enhanced immunogenicity and protection study of lipid modified protein vaccine candidates of Nontypeable Haemophilus influenzae (1R21AI153936-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10042550. Licensed CC0.

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