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*
Laboratory of Parasitic Biology and Biochemistry and
Division of Veterinary Medicine, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852;
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892;
§
Preclinical Research and Development, Genetics Institute, Andover, MA 01810; and
¶
Biotechnology Unit, Biobrás, Montes Claros, Brazil
Protection from cutaneous leishmaniasis, a chronic ulcerating skin
lesion affecting millions, has been achieved historically using live
virulent preparations of the parasite. Killed or recombinant Ags that
could be safer as vaccines generally require an adjuvant for induction
of a strong Th1 response in murine models. Murine rIL-12 as an adjuvant
with soluble Leishmania Ag has been shown to protect
susceptible mice. We used 48 rhesus macaques to assess the safety,
immunogenicity, and efficacy of a vaccine combining heat-killed
Leishmania amazonensis with human rIL-12 (rhIL-12) and
alum (aluminum hydroxide gel) as adjuvants. The single s.c. vaccination
was found to be safe and immunogenic, although a small transient s.c.
nodule developed at the site. Groups receiving rhIL-12 had an augmented
in vitro Ag-specific IFN-
response after vaccination, as well as
increased production of IgG. No increase in IL-4 or IL-10 was found in
cell culture supernatants from either control or experimental groups.
Delayed hypersensitivity reactions were not predictive of protection.
Intradermal forehead challenge infection with 107
metacyclic L. amazonensis promastigotes at 4 wk
demonstrated protective immunity in all 12 monkeys receiving 2 µg
rhIL-12 with alum and Ag. Partial efficacy was seen with lower doses of
rhIL-12 and in groups lacking either adjuvant. Thus, a single dose
vaccine with killed Ag using rhIL-12 and alum as adjuvants was safe and
fully effective in this primate model of cutaneous leishmaniasis. This
study extends the murine data to primates, and provides a basis for
further human trials.
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