The potency and durability of DNA- and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge

DNA- and protein- based vaccines against cutaneous leishmaniasis due to Lei shmania major were evaluated using a challenge model that more closely repr oduces the pathology and immunity associated with sand fly-transmitted infe ction. C57BL/6 mice were vaccinated s.c. with a mixture of plasmid DNAs enc oding the Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or with autoclaved L major promastigotes (ALM) plus rIL-12, and the mice were challenged by in oculation of 100 metacyclic promastigotes in the ear dermis. When challenge d at 2 wk postvaccination, mice receiving AgDNA or ALM/rIL-12 were complete ly protected against the development of dermal lesions, and both groups had a 100-fold reduction in peak dermal parasite loads compared with controls. When challenged at 12 wk, mice vaccinated with ALM/rIL-12 maintained parti al protection against dermal lesions and their parasite loads were no longe r significantly reduced, whereas the mice vaccinated with AgDNA remained co mpletely protected and had a 1000-fold reduction in dermal parasite loads. Mice vaccinated with AgDNA also harbored few, if any, parasites in the skin during the chronic phase, and their ability to transmit L major to vector sand flies was completely abrogated. The durable protection in mice vaccina ted with AgDNA was associated with the recruitment of both CD8(+) and CD4() T cells to the site of intradermal challenge and with IFN-gamma productio n by CD8(+) T cells in lymph nodes draining the challenge site. These data suggest that under conditions of natural challenge, DNA vaccination has the capacity to confer complete protection against cutaneous leishmaniasis and to prevent the establishment of infection reservoirs. The Journal of Immun ology, 2001.