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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Characterization and evaluation of the Moraxella catarrhalis oligopeptide permease A as a mucosal vaccine antigen
Min Yang1, Antoinette Johnson, Timothy F Murphy
1Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, NY 14203, USA.
Abstract:
Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis.
Insights
Oligopeptide permease protein A (OppA) is a promising vaccine candidate against Moraxella catarrhalis. This highly conserved bacterial protein elicits protective immune responses in mice, suggesting its potential for preventing infections in children and adults.
Area of Science:
- Bacteriology
- Vaccinology
- Immunology
Background:
- Moraxella catarrhalis causes significant pediatric otitis media and adult chronic obstructive pulmonary disease exacerbations.
- Development of a vaccine against M. catarrhalis is crucial for vulnerable populations.
Purpose of the Study:
- To identify and evaluate potential vaccine antigens for M. catarrhalis.
- To assess the immunogenicity and protective potential of oligopeptide permease protein A (OppA).
Main Methods:
- Genome mining identified OppA as a conserved antigen.
- Recombinant OppA was expressed and purified; an oppA knockout mutant was created.
- Mice were immunized intranasally with OppA, and immune responses were analyzed.
Main Results:
- OppA is highly conserved across M. catarrhalis clinical isolates.
- Antibodies to OppA recognized bacterial surface epitopes and native protein.
- Intranasal OppA immunization induced systemic and mucosal immunity and enhanced bacterial clearance in mice.
Conclusions:
- OppA is a conserved, immunogenic M. catarrhalis protein with surface-exposed epitopes.
- OppA vaccination in mice demonstrated protective immune responses.
- OppA warrants further investigation as a vaccine antigen against M. catarrhalis infections.
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