Characterization and evaluation of Haps as a vaccine candidate against nontypable Haemophilus influenzae

The Haemophilus influenzae Hap protein is an autotransporter serine protease that has intimate interaction with human epithelial cells. Hap contains an extracellular adhesive and protease domain called Hap, and an outer membrane associated translocator domain called Hap(s). Transmission electron microscopy using gold-labeled anti-Hap antibodies showed that Hap protein was expressed at various levels on the surface of different NTHi strains. Hap(s) specific anti-sera cross reacted with heterologous strains of NTHi in a whole cell ELISA and blocked Hap-mediated attachment to human epithelial cells. BALB/c mice immunized intranasally (IN) with Hap(s) mixed with a genetically detoxified cholera toxin, CT-E29H [1], and challenged IN with a heterologous strain, showed significantly reduced levels of colonization in the nasopharynx of immunized mice.