The nonacylated form of
protein D (PDm) of Haemophilus influenzae has been shown to induce the production of
antibodies that are bactericidal to homologous and heterologous nontypeable H. influenzae (NTHi) strains. In this study, immunization of rats with
lipoprotein D (LPD) induced higher levels of anti-
protein D
immunoglobulin G and A serum
antibodies than immunization with PDm, and the bactericidal activities of sera from LPD-immunized rats were greater than those of sera from PDm-immunized rats. Immunization with LPD or PDm did not prevent the development of acute
otitis media (AOM) when rats were challenged with 10(4) CFU of an NTHi strain. However, on the eighth day of bacterial challenge, 50% (5 of 10) of LPD-immunized rats had recovered from
otitis media and 30% (3 of 10) had negative middle ear cultures, whereas only 30% (3 of 10) of PDm-immunized rats had recovered, though none was culture positive. Immunization with an inactivated homologous bacterial strain elicited 70% protection (i.e., 7 of 10 rats) in the rat
otitis media model. LPD and PDm were also conjugated to the H. influenzae type b (Hib) capsular
polysaccharide, polyribosyl
ribitol phosphate (PRP), to test
protein D-conjugated PRP
vaccine's potential for protection against
Hib infection. When two LPD-conjugated and two PDm-conjugated PRP
vaccines, each containing a different
protein concentration, and a
tetanus toxoid-conjugated
vaccine (ACT-HIB) were tested in the experimental model of rat
otitis induced with a Hib strain (Minn A), both of the LPD-conjugated and one of the PDm-conjugated
vaccines induced significant protection from AOM, the level of protection being highest in animals given the
vaccine with the highest LPD content. Sera from these rats also manifested the highest anti-PRP and anti-LPD antibody levels and the highest bactericidal activities against a Hib strain and an NTHi strain.