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Haemophilus ducreyi , the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbA I ) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbA I dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HP hgbA I and 35000HP hgbA II , respectively). Pigs immunized with the nHgbA I /MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HP hgbA I but not heterologous strain 35000HP hgbA II , as evidenced by the isolation of only strain 35000HP hgbA II from nHgbA I -immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbA I -immunized animals challenged with strains 35000HP hgbA I but not those challenged with strain 35000HP hgbA II . Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbA I /MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbA I /Freund's vaccine; however, anti-nHgbA I from both studies bound whole cells of 35000HP hgbA I better than 35000HP hgbA II and partially blocked hemoglobin binding to nHgbA I . In conclusion, despite eliciting lower antibody ELISA activity than the nHgbA I /Freund's, the nHgbA I /MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi , suggesting that a bivalent HgbA vaccine may be needed.

Haemophilus ducreyi , the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi , only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme.