Cutaneous leishmaniasis still affects about 10 million people a year, despite numerous attempts at vector control, parasite eradication, and creation of various vaccine formulations. Solid immunity develops after natural infection in humans with all cutaneous species. Vaccination against the disease with living parasites, or leishmanization, has only been tried in areas where cutaneous leishmaniasis is endemic. The lesion induced is often complicated by prolonged ulceration and scarring since live parasites are used. Vaccination with killed preparations has only been shown to be immunogenic in small numbers of people, and has never been shown to be effective in large trials. Recent observations using the mouse model have shown that Interleukin-12 can reverse the immune response of susceptible BALB/c mice when used as an adjuvant with a crude leishmania vaccine preparation. With the cooperation of the Genetics Institute (Cambridge, MA), which makes recombinant human and murine IL-12, and B!obras (Montes Claros, Brazil), which makes a leishmania vaccine and skin test antigen, we are developing a product for use in a human Phase I/II trial. These studies are intended to be a proof-of-concept alone. It is anticipated that one of the several recombinant leishmania antigens under development at other laboratories will be ready for human trials within the next year or two. While the mouse model has shown several antigens to be efficacious when combined with IL-12, there is an urgent need to confirm the potential for vaccination in humans with the cytokine adjuvant, and to assure the community of the safety and immuno-genicity of a crude preparation. We have just completed a series of experiments using mice to test the safety, potency, efficacy, and stability of several preparations. The vaccine antigen is made from cultures of parasites that are washed, then frozen and thawed several times to break the cells. These crude leishmania preps were shown to work well despite autoclaving, and the autoclaved preparation remains stable after one month at 37 degrees. Monkey experiments will start next month to evaluate the safety, immunogenicity, and efficacy of the autoclaved preparation with rHuIL-12 as an adjuvant. We plan to submit an IND for the combination of the products and begin the clinical trials at NIH by the end of the year.
