Prevalence of, antibody response to, and immunity induced by Haemophilus ducreyi hemolysin

Haemophilus ducreyi, the etiologic agent of chancroid, a genital ulcer dise ase, produces a cell-associated hemolysin whose role in virulence is not we ll defined. Hemolysin is encoded by two genes, hhdA and hhdB, which, based on their homology to Serratia marcescens shlA and shlB genes, are believed to encode the hemolysin structural protein and a protein required for secre tion and modification of this protein, respectively. In this study, we dete rmined the prevalence and expression of the hemolysin genes in 90 H. ducrey i isolates obtained from diverse geographic locations from 1952 to 1996 and found that all strains contained DNA homologous to the hhdB and hhdA genes . In addition, all strains expressed a hemolytic activity. We also determin ed that hemolysin is expressed in vivo and is immunogenic, as indicated by the induction of antibodies to hemolysin in both the primate and rabbit dis ease models as well as in human patients with naturally acquired chancroid. Wild-type strain 35000 and isogenic hemolysin-negative mutants showed no d ifference in lesion development in the temperature dependent rabbit model. However, immunization of rabbits with the purified hemolysin protein reduce d the recovery of wild-type H. ducreyi, but not hemolysin-negative mutants, from lesions. Our study indicates that hemolysin is a possible candidate f or vaccine development due to its immunogenicity, expression in vitro and i n vivo by most, if not all, strains, and the effect of immunization on redu cing the recovery of viable H. ducreyi in experimental disease in rabbits.