History, Research, and Development  
Vaccine Research: Progress and Challenges

Although a Leishmaniasis vaccine has not yet been approved for general use , as the research in this area has advanced there have been a number of important milestones made along the way. These milestones are largely due to the findings of animal models as well as CLINICAL TRIALS which have demonstrated moderate success in sample populations with respect to immunization against Leishmania infection. Furthermore, other innovative approaches to combating Leishmaniasis are being explored and are discussed in the CURRENT DEVELOPMENTS section. It is important however to acknowledge that there are a number of challenges that are impeding vaccine development. Thus a summary of the major progress and challenges in the cummulative research follows.

While the precise mechanism of the immune response to a Leishmania sp. infection is not completely understood it has been discovered that acquired resistance to leishmaniasis is mediated by a host of immune cells. Furthermore it has been observed that upon mounting an immune response, a dominance of Th-1 Lymphocytes is related to disease regression whereas a dominance of Th-2 Lymphoctyes is related to disease progression. In particular production of Interferon gamma (IFN-γ) and IL-2 is especially correlated to the healing of lesions and ulcerations. However, complicating the ability of researches to understand the immune response is the role of genetic variation in humans. Furthermore, it is important to note that there is variation (in terms of which immune cells are more heavily involved in an immune response) that has been observed between cases of Cutaneous and Mucocutaneous Leishmaniasis and cases of Visceral Leishmaniasis. This variation is underscored by the virulence of the Leishmania genus. Antigenic variation between Leishmania species makes it extremely difficult to predict which antigens will be effective at inducing an appropriate immune cell response. Thus future vaccine development attempts to address this challenge by incorporating combinations of multiple components of the parasite into the final vaccine. The most notable research in this vein is currently being funded by the Bill & Melinda Gates Foundation, and seeks to develop the polyprotein Leish-111f comprised of recombinant antigens (TSA, LeIF, LmSTI-1) in the presence of various adjuvants (Monophosphoryl Lipid A and Squalene Oil).