The fourth surface-exposed region of the outer membrane protein P5-homologous adhesin of nontypable Haemophilus influenzae is an immunodominant but nonprotective decoying epitope.
Nontypable Haemophilus influenzae is a major cause of otitis media and other mucosal infections. After natural disease in children and experimental disease in chinchillas, we found a hierarchical pattern of immunodominance among the four surface-exposed regions of the P5-homologous adhesin, with the greatest response directed to region 4. However, Ab to region 4 is not protective. When this natural but biased response was refocused to region 3 by immunization, augmented bacterial clearance and protection from ascending otitis media was observed. Collectively, the data indicate that region 4 contains a highly immunodominant but nonprotective decoying epitope, the presence of which dampens the immune response to a subdominant but protective epitope in region 3.
Novotny
Laura A
LA
Division of Molecular Medicine, Department of Pediatrics, Columbus Children's Research Institute, Ohio State University College of Medicine and Public Health, Columbus, OH 43205, USA.
Bakaletz
Lauren O
LO
D000208:Acute Disease; D018829:Adhesins, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015373:Bacterial Typing Techniques; D002462:Cell Membrane / Q000276:immunology / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D002682:Chinchilla; D004195:Disease Models, Animal; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology; D006193:Haemophilus influenzae / Q000737:chemistry / Q000145:classification* / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007223:Infant; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018073:Haemophilus Vaccines; D016056:Immunodominant Epitopes; C082912:outer membrane protein P5, Haemophilus