A P5 peptide that is homologous to peptide 10 of OprF from Pseudomonas aeruginosa enhances clearance of nontypeable Haemophilus influenzae from acutely infected rat lung in the absence of detectable peptide-specific antibody.
Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen associated with otitis media and the exacerbation of chronic bronchitis. This study reports the vaccine potential of three peptides representing conserved regions of the NTHi P5 outer membrane protein which have been fused to a promiscuous measles virus F protein T-cell eptitope (MVF). The peptides correspond to a region in surface loop one (MVF/L1A), the central region of loop four (MVF/L4), and a C-terminal region homologous to peptide 10 of OprF from Pseudomonas aeruginosa (MVF/H3). Immunization of rats with MVF/H3 was the most efficacious in significantly reducing the number of viable NTHi in both the broncho-alveolar lavage fluid (74%) and lung homogenates (70%), compared to control rats. Importantly, despite significantly increased rates of clearance, immunization with MVF/H3 elicited poor antibody responses, suggesting that cell-mediated rather than humoral responses play an important role in the enhanced clearance of NTHi in this model.
Webb
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The Gadi Research Center, Faculty of Applied Science and Design, University of Canberra, Canberra City, Australian Capital Territory 2601, Australia. Dianne.Webb@anu.edu.au
Cripps
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D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000378:metabolism; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000276:immunology* / Q000382:microbiology*; D018073:Haemophilus Vaccines / Q000235:genetics / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology / Q000472:pathogenicity*; D007114:Immunization; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics* / Q000276:immunology; D018272:Porins / Q000235:genetics* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D018073:Haemophilus Vaccines; D010455:Peptides; D018272:Porins; D011993:Recombinant Fusion Proteins; C078167:OMPA outer membrane proteins