Local and systemic antibody levels against protein D of Haemophilus influenzae following immunization and infection in rats

Outer membrane proteins of Haemophilus influenzae are considered as possible vaccine candidates against non-typable H. influenzae (NTHi), a major cause of respiratory infections. Here, we study local and systemic antibody responses to protein D, a well-conserved 42-kDa membrane protein, following local and systemic immunization, and experimental acute otitis media (AOM) with NTHi and H. influenzae type b (Hib) in rats. Animals that were challenged and rechallenged in the middle ear with Hib strain Minn A or NTHi strain 1161 developed IgG and IgA antibodies in serum but not in middle ear lavage (MEL) material or saliva. In contrast, following per oral immunization with NTHi strain 772 and Escherichia coli JM83 (pHIC348) (containing protein D gene) and, to a lesser degree after intranasal inoculation of NTHi strain 772, high saliva IgA antibodies to protein D developed, but there was no rise in antibodies to protein D in the MEL material or the sera of these animals. These results show that protein D can elicit different systemic and local antibody responses depending on the site of delivery and the form of administration. Furthermore, experimental AOM with NTHi and Hib induces systemic IgG and IgA antibodies to protein D but fails to induce a mucosal immune response.