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.