Characterization and evaluation of the Moraxella catarrhalis oligopeptide permease A as a mucosal vaccine antigen.
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.
Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, NY 14203, USA.
Min
M
Yang
Antoinette
A
Johnson
Timothy F
TF
Murphy
D058956:Administration, Mucosal; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology / Q000517:prevention & control; D026901:Membrane Transport Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D001936:Moraxella catarrhalis / Q000201:enzymology*; D045828:Moraxellaceae Infections / Q000517:prevention & control*; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D026901:Membrane Transport Proteins; C037230:oligopeptide permease, Bacteria