Vaccination against Leishmania infections

Leishmaniasis, that affects millions of people worldwide, is an infectious disease caused by the protozoan parasite Leishmania. Incidence of the condition appears to be increasing in several parts of the world. Of the three main presentations of the disease, i.e. cutaneous, mucocutaneous and visceral, only the first one tends to heal spontaneously, while the other two are considered fatal if left to run their natural course. Recovery from leishmaniasis, whether spontaneous or drug-induced, is usually accompanied by solid immunity against reinfection, which provides a rationale for attempting to design vaccines against the disease. This review presents an outline of the main immunological features of Leishmania infections and of the mechanisms thought to operate in recovery from the disease. It describes various experimental approaches to vaccination in man and animal models, including the use of virulent and avirulent organisms, of dead parasites and extracts thereof, and of purified parasite proteins. Assays using novel technologies, such as the direct injection of DNAs encoding parasite proteins, or the inoculation of viral or bacterial vectors expressing such molecules, as well as recent experiments aimed at inducing an immune response against saliva of the insect vector, are also reviewed. Observations made during the course of these studies have reinforced the notion that vaccination against leishmaniasis is indeed feasible. However, in spite of intensive efforts by many groups and many reports of success in man and in animal models, a consensus is yet to emerge as to what constitutes the best approach to vaccination against leishmaniasis.