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 several pharmaceutical companies, we are developing a product for use in human clinical trials. 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 completed a series of experiments using mice and rhesus macaques to test the safety, potency, efficacy, and stability of several preparations. The vaccine antigen was made in our labs 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!C. An IND has been submitted for the Phase I/II clinical trial, which should be completed by the end of the year. Preclinical studies for other vaccine strategies have been initiated including DNA vaccination and the use of CpG oligonucleotides as an adjuvant.
