Vervet monkeys vaccinated with killed Leishmania major parasites and interleukin-12 develop a type 1 immune response but are not protected against challenge infection.
Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-gamma) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 microg), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At higher doses of IL-12 (30 microg), a substantial increase in Leishmania-specific immune responses was observed, and monkeys immunized with antigen and IL-12 exhibited an IFN-gamma response that was as great as that in animals that had resolved a primary infection and were immune. Nevertheless, despite the presence of correlates of protection, the disease course was only slightly altered, and protection was low compared to that in self-cured monkeys. These data suggest that protection against leishmaniasis may require more than the activation of Leishmania-specific IFN-gamma-producing T cells, which has important implications for designing a vaccine against leishmaniasis.
Gicheru
M M
MM
Institute of Primate Research, Nairobi, Kenya.
Olobo
J O
JO
Anjili
C O
CO
Orago
A S
AS
Modabber
F
F
Scott
P
P
D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D018664:Interleukin-12 / Q000494:pharmacology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014611:Vaccination
D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12