# Novel immunotherapeutics for the management of otitis media due to H. influenzae

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $574,522

## Abstract

PROJECT SUMMARY
There have been tremendous recent advances in our understanding of the pathogenesis of otitis media (OM)
due to nontypeable Haemophilus influenzae (NTHI). Significantly, we’ve come to appreciate the role that
biofilms play in both post-tympanostomy tube otorrhea as well as in the chronicity and recurrence of NTHI-
induced OM. Bacteria dwelling within a biofilm present a formidable obstacle to effectors of immunity and
antibiotic therapies. Thereby, in order to design novel and effective strategies to better treat and/or prevent
otorrhea and OM, it is necessary to understand both the biology of biofilms, including their unique biochemical
and proteomic composition, as well as how one might undermine these structures to mediate a therapeutic
‘cure’. Through the successful conduct of a series of three highly integrated Specific Aims, we will expand upon
a solid foundation of a growing body of literature from our laboratories which show that we can target a family
of bacterial DNA-binding proteins (IHF and HU) that are critical to stabilize extracellular DNA (eDNA) present
within an NTHI biofilm to reduce or eradicate that structure both in vitro and in vivo. Here, we will now identify
and characterize the best therapeutic antigenic targets within both IHF and HU, with a focus on specific
functional domains. We will also determine both the kinetics of release and the availability of IHF and HU
subunits within the NTHI eDNA-DNABII dependent extracellular matrix in order to identify an optimal
therapeutic window for intervention. Moreover, we will determine the therapeutic value of using biofilm-focused,
epitope-targeted monoclonal antibodies and cocktails thereof to resolve biofilms associated with chronic
otorrhea and otitis media. These latter studies will first be conducted in vitro using both monospecies biofilms,
as well as those of mixed otopathogen etiology, to better reflect the clinical condition. Finally, we will
determine the relative therapeutic efficacy of this approach in vivo, using a chinchilla model of experimental
OM. The chinchilla represents an anatomically appropriate, robust, reproducible and extensively studied
animal model of this highly prevalent pediatric biofilm disease in which to conduct these essential pre-clinical
studies. Importantly, whereas our primary target for disease intervention is OM, because NTHI causes many
biofilm-associated diseases of the human respiratory tract, the studies proposed here will also likely provide a
basis for the design of better practices to treat disease in other parts of the airway such as the sinuses (chronic
rhinosinusitis), the tonsils and adenoids (tonsillitis, adenoiditis), the bronchus (chronic cough and bronchitis)
and the lung (COPD, early stage CF, community acquired pneumonia). Our Specific Aims are perfectly
aligned with both Healthy People 2020 (Hearing and Other Sensory or Communication Disorders, ENT-VSL-2:
“Reduce otitis media in children and adolescents”), ...

## Key facts

- **NIH application ID:** 9989097
- **Project number:** 5R01DC011818-10
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Lauren O Bakaletz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $574,522
- **Award type:** 5
- **Project period:** 2011-07-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989097

## Citation

> US National Institutes of Health, RePORTER application 9989097, Novel immunotherapeutics for the management of otitis media due to H. influenzae (5R01DC011818-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989097. Licensed CC0.

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