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Infect Immun. 2018 Feb 20;86(3). pii: e00652-17. doi: 10.1128/IAI.00652-17. Print 2018 Mar.

Mapping Protective Regions on a Three-Dimensional Model of the Moraxella catarrhalis Vaccine Antigen Oligopeptide Permease A.

Author information

1
Clinical and Translational Research Center, University at Buffalo, the State University of New York, Buffalo, New York, USA.
2
Division of Infectious Diseases, Department of Medicine, University at Buffalo, the State University of New York, Buffalo, New York, USA.
3
Department of Biostatistics, University at Buffalo, the State University of New York, Buffalo, New York, USA.
4
Department of Structural Biology, University at Buffalo, the State University of New York, Buffalo, New York, USA.
5
Hauptman Woodward Medical Research Institute, Buffalo, New York, USA.
6
Clinical and Translational Research Center, University at Buffalo, the State University of New York, Buffalo, New York, USA murphyt@buffalo.edu.
7
Department of Microbiology, University at Buffalo, the State University of New York, Buffalo, New York, USA.

Abstract

A vaccine against Moraxella catarrhalis would reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is (i) a nutritional virulence factor expressed on the bacterial cell surface during infection, (ii) widely conserved among strains, (iii) highly immunogenic, and (iv) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals after pulmonary challenge. To identify regions of OppA that bind protective antibodies, truncated constructs of OppA were engineered and studied to map regions of OppA with surface-accessible epitopes that bind high-avidity antibodies following vaccination. Protective epitopes were located in the N and C termini of the protein. Immunization of mice with constructs corresponding to these regions (T5 and T8) induced protective responses. Studies of overlapping peptide libraries of constructs T5 and T8 with OppA immune serum identified two discrete regions on each construct. These potentially protective regions were mapped on a three-dimensional computational model of OppA, where regions with solvent-accessible amino acids were identified as three potentially protective epitopes. In all, these studies revealed two regions with three specific epitopes in OppA that induce potentially protective antibody responses following vaccination. Detection of antibodies to these regions could serve to guide vaccine formulation and as a diagnostic tool for monitoring development of protective responses during clinical trials.

KEYWORDS:

COPD; Moraxella catarrhalis; OppA; otitis media; surface antigens; vaccines

PMID:
29203544
PMCID:
PMC5820933
DOI:
10.1128/IAI.00652-17
[Indexed for MEDLINE]
Free PMC Article

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