Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

Abstract

SUMMARYIn this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

“…Ultimately, activation of TLR-4 not only triggers innate immunity, but also enhances both humoral and cellular immune responses [63,64]. Recently, Mutiso et al [65] indicated good safety levels of a vaccine comprising L. donovani sonicate antigen delivered with either monophosphoryl lipid A or montanide ISA 720 in the vervet monkey model. Saponins are natural glycosides of steroid or triterpene, which are known to activate immune system.…”

Evaluation of in vitro and in vivo antileishmanial potential of bergenin rich Bergenia ligulata (Wall.) Engl. root extract against visceral leishmaniasis in inbred BALB/c mice through immunomodulation

“…In contrast, predominant Th2 type of immune response is characterized by higher levels of IL-10 and IL-4. 26 IL-12 is secreted by antigen-presenting cells i.e. macrophages which further stimulate the proliferation of CD4 + Th1 cells.…”

Cell Immune Response in Mice Skin Stimulated with Different Adjuvants by Intradermal Route

“…GLA-SE, used in a vaccine against the Influenza virus, stimulated an increase of humoral and cellular immune response with induction mainly of TNF-α and IFN-γ cytokines [6]. Montanide ISA 720 was evaluated associated with Leishmania donovani antigen, inducing a strong Delayed-Type Hypersensitivity (DTH) response, with the production of TNF-α and IFN-γ [7]. R-848 was also able to induce a type 1 immune response, with activation of myeloid and plasmacytoid dendritic cells, lymphocytes, and macrophages [8,9].…”