Haemophilus influenzae represents a common cause of human disease and an important source of morbidity and mortality. Disease caused by this organism begins with colonization of the upper respiratory tract. Several studies indicate that H. influenzae is capable of binding to and entering cultured human cells, properties which are potentially of relevance to the process of colonization. In the present study, we isolated an H. influenzae gene designated hap, which is associated with the capacity for in vitro attachment and entry. Analysis of the derived amino acid sequence of hap demonstrated significant homology with the serine-type IgA1 proteases expressed by H. influenzae and Neisseria gonorrhoeae. It is notable that the hap product shares the catalytic domain of the IgA1 proteases and appears to be processed and secreted in an analogous manner. We speculate that the hap gene product is an important determinant of colonization, perhaps enabling the organism to evade the local immune response and thereby persist within the respiratory tract.

Nontypable Haemophilus influenzae is a common cause of human disease and is associated with significant morbidity and considerable societal cost. At present, measures to prevent nontypable H. influenzae disease are limited to prophylactic antibiotics and, on occasion, exogenous antibody preparations. However, because these interventions are often inadequate, there is interest in developing an effective vaccine. Given the marked diversity among epidemiologically unrelated strains and the frequent strain specificity of the immune response to infection, efforts have focused on identifying bacterial antigens that are highly conserved and capable of stimulating protective antibody. With the recent identification of several such antigens, attention must now turn toward selecting the appropriate combination of these molecules and determining the optimal strategy for their presentation to the immune system. The ultimate goal is to induce broad-based and long-lasting protection.

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