Abstract

Nontypeable Haemophilus influenzae (NTHi) is one of the major organisms in the upper respiratory nasopharyngeal microbiota. In addition to its role as a commensal in the nasopharynx, NTHi is also the cause of sinusitis, pneumonia, and meningitis. Most relevant to this work, NTHi is one of the major causes of otitis media (OM), an inflammatory disease of the middle ear that affects 65-300 million children globally each year. In the US, acute OM (AOM or ear infection) is the most common reason for prescribed antibiotics. Due to the dramatic increase in antibiotic resistant strains of bacteria, there is currently an urgent need for alternative treatments for NTHi. After decades of studies, several proteins have risen to the top as potential protein vaccine candidates for NTHi. P6, Protein D, and OMP26 are three such NTHi proteins, which have been shown to be immunogenic in young children. We proposed to test all three vaccine candidates as a single trivalent vaccine formulation and as individual protein vaccines for protection against AOM using a mouse model. This work describes our efforts to develop a robust AOM mouse model for the assessment of protein vaccines, as well as our protein vaccine study which employed that model. The results of our study suggest that Protein D, Omp26, and P6 all elicit protection against colonization of NTHi in the ear, and the best protection occurs when all three proteins are contained within a single formulation. We also describe a surprising finding that two of the proteins interact in vivo, yielding one of the proteins ineffective at eliciting an antibody response.

Publication Date

5-2018

Document Type

Thesis

Student Type

Graduate

Degree Name

Chemistry (MS)

Department, Program, or Center

School of Chemistry and Materials Science (COS)

Advisor

Lea Vacca Michel

Advisor/Committee Member

Ravinder Kaur

Advisor/Committee Member

André Hudson

Comments

This thesis is embargoed for one year. Full-text will be available on or around 5/8/19.

Campus

RIT – Main Campus

Available for download on Wednesday, May 08, 2019

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