Vaccine Studies of the hemoglobin receptor of H. ducreyi

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DESCRIPTION (provided by applicant): Haemophilus ducreyi, the etiologic agent of the genital ulcer disease chancroid, is a significant public health problem in several regions worldwide. In Africa, Asia and other developing countries, it is an important cofactor for the heterosexual transmission of HIV. Control of chancroid, using an effective vaccine that is properly administered, would likely reduce HIV transmission. It is the goal of my laboratory to develop such a vaccine. We propose studies on the immunobiology and structure of the hemoglobin receptor (HgbA) of H. ducreyi. Several attributes of HgbA make it an attractive vaccine candidate. HgbA is required to establish human experimental infection. HgbA is conserved immunologically and functionally and all H. ducreyi express it. Unlike hemoglobin receptors from other bacteria, HgbA does not undergo phase or antigenic variation. Studies in the chilled rabbit model of chancroid infection, suggest purified native HgbA or recombinantly expressed HgbA are partially effective vaccines. Further vaccine studies utilizing the Swine model of H.ducreyi infection, that more closely resembles natural human infection. Experimental vaccines will consist of purified native HgbA from H. ducreyi type strain 35000, or possibly synthetic peptides derived from HgbA. We will test the ability of native HgbA to protect against a homologous and heterologous challenge infection. Detailed studies will be undertaken on HgbA including understanding its structure and regions/residues of HgbA that are surface-exposed. We will determine the variability of the HgbA protein from geographically diverse isolates. These studies are important for better understanding of chancroid pathogenesis and will facilitate vaccine development in several aspects.