Leishmaniasis Vaccination

In the history of vaccine development, key observations have gradually led to our ability to take rational approaches toward the induction of protective immunity to microbial pathogens. The earliest efforts consisted of inoculating lesion material into healthy individuals resulting in the then inexplicable prevention of the development of similar disease. Centuries later, after researchers found that microscopic forms were responsible for the major human diseases such as tuberculosis and smallpox, vaccines consisting of inoculating weakened or attenuated organisms were developed. The discovery of the cell populations that mediate antibody and cellular immune responses, followed by the identification of the cytokine mediators of cellular immunity and the ability to identify, isolate, purify, and produce antigenic molecules of various pathogens has permitted a rational approach toward vaccine development. Perhaps no disease model has been more widely used to understand the roles of cell populations and cytokines in mediating disease susceptibility and resistance than the infection of inbred mice with the Leishmania parasite 1. For example, BALB/c mice infected subcutaneously with Leishmania major develop nonhealing, disseminated, fatal infections, whereas C57BL mice similarly infected are more resistant, and heal their infections. In addition to susceptibility factors determined by host genetics, it has recently been appreciated that the insect that transmits leishmania to humans may play a key role in the establishment of infection. The study by Valenzuela et al. in this issue 2 exploits this information in what may prove to be a unique approach to vaccination.