Current status and perspectives of the immunotherapy of leishmaniasis

There is still a need for innovative and alternative therapies against leishmaniasis. Despite recent advances in immunology, effective immunotherapy against the disease has not yet been proven. Live, attenuated and dead parasites, purified and recombinant specific antigens, DNA vaccines as well as DC-based immunization that have been employed in the development of protective vaccine have not yet been adopted as immunotherapeutic agents. Recently, a commercially prophylactic vaccine (Leish-110f) was developed by BioPharm International, by constructing a recombinant fusion protein consisting of TSA (thiol-specific antioxidant), LmSTI1 (L. major stress-inducible protein 1) and LeIF (Leishmania elongation initiation factor). This vaccine, when administered together with the adjuvant monophosphoryl lipid A (MPL), either alone or plus squalene (MPL-SE) or AdjuPrime, protected mice against L. major and L. infantum infections. Also, Leishvacin (Leishvacin, Biobrs, Montes Carlos, State of Minas Gerais, Brazil), a commercial non-living promastigote polyvalent Leishmania vaccine administered either alone or combined with BCG, was found to be highly immunogenic against American CL in humans. Leishvacin alone was also found to be effective as a prophylactic vaccine, sensitizing lymphocytes from normal uninfected humans, which was further accelerated by recombinant GM-CSF. Standardization and additional carefully controlled studies in animals and humans, using these new vaccines and other immunomodulators in conjunction with various chemotherapeutic agents, are still required to determine the optimal conditions for the development of a potent anti-leishmanial immunotherapy and immunochemotherapy.