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Laboratory of Parasitic Diseases and
Laboratory of Clinical Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Corixa Corp., Seattle, WA 98104; and
Infectious Disease Research Institute, Seattle, WA 98104
DNA- and protein- based vaccines against cutaneous leishmaniasis
due to Leishmania major were evaluated using a challenge
model that more closely reproduces the pathology and immunity
associated with sand fly-transmitted infection. C57BL/6 mice were
vaccinated s.c. with a mixture of plasmid DNAs encoding the
Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or
with autoclaved L. major promastigotes (ALM) plus
rIL-12, and the mice were challenged by inoculation of 100 metacyclic
promastigotes in the ear dermis. When challenged at 2 wk
postvaccination, mice receiving AgDNA or ALM/rIL-12 were completely
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 partial protection against dermal lesions and their parasite
loads were no longer significantly reduced, whereas the mice vaccinated
with AgDNA remained completely 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 vaccinated with
AgDNA was associated with the recruitment of both CD8+ and
CD4+ T cells to the site of intradermal challenge and with
IFN-
production 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.
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