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Mapping Protective Regions on a Three-Dimensional Model of the Moraxella catarrhalis Vaccine Antigen Oligopeptide Permease A.
- Source :
-
Infection and immunity [Infect Immun] 2018 Feb 20; Vol. 86 (3). Date of Electronic Publication: 2018 Feb 20 (Print Publication: 2018). - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 American Society for Microbiology.)
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Bacterial immunology
Bacterial Proteins genetics
Bacterial Vaccines genetics
Epitope Mapping
Humans
Male
Membrane Transport Proteins genetics
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Moraxella catarrhalis chemistry
Moraxella catarrhalis genetics
Moraxella catarrhalis immunology
Moraxellaceae Infections immunology
Otitis Media immunology
Otitis Media microbiology
Bacterial Proteins chemistry
Bacterial Proteins immunology
Bacterial Vaccines chemistry
Bacterial Vaccines immunology
Membrane Transport Proteins chemistry
Membrane Transport Proteins immunology
Moraxella catarrhalis enzymology
Moraxellaceae Infections microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 86
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 29203544
- Full Text :
- https://doi.org/10.1128/IAI.00652-17