Subcutaneous immunization against Leishmania major - infection in mice: efficacy of formalin-killed promastigotes combined with adjuvants

Abstract

SUMMARYFormalin-killed promastigotes (FKP) of Leishmania major, in combination with Montanide ISA 720 (MISA), BCG or alum were used in vaccination of an inbred murine model against cutaneous leishmaniasis (CL). Significant and specific increases in anti-FKP IgG responses were detected for both alum-FKP and BCG-FKP compared to MISA-FKP (p < 0.001). Significant increases in splenic lymphocyte recall proliferation was obtained in the MISA-FKP vaccinated mice compared to alum-FKP or BCG-FKP vaccinated groups (p < 0.01). The highest interferon-γ responses were observed in the BCG-FKP group followed by the MISA-FKP while the alum-FKP gave the least responses. Significantly reduced lesion sizes were obtained in the MISA-FKP group compared to the BCG/ alum adjuvants-FKP vaccinated groups. Although the BCG-FKP group showed the highest IFN-γ responses, it failed to control cutaneous lesions. Significant reductions in parasite numbers were observed in the MISA-FKP and BCG-FKP vaccinated groups (p < 0.001). There was a good correlation between parasite burden and IFN-γ level indicating IFN-γ response as a sensitive parameter of the immune status. In conclusion, MISA-FKP is the most efficacious vaccine formulation against murine cutaneous leishmaniasis.

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

“…However, as a matter of serious concern, the study has established that, based on adverse local skin reaction, an immunization containing BCG is not safe as it is associated with erythematous ulcerative skin nodules or indurations. This confirms the results observed in our earlier study on mice (MUTISO et al, 2010b) where vaccination with BCG was associated with adverse reaction. Other studies involving the use of the monkey system have also associated BCG with severe reactions (MISRA et al, 2001).…”

“…In malaria, HIV and cancer vaccine studies, MISA 720 has been indicated to induce high Th1 immune responses important for the control of these diseases (KENNEY & ELDELMAN, 2003). This adjuvant has also been shown to induce strong Th1 cytokine in Leishmania vaccination studies (MASINA et al, 2003;MUTISO et al, 2010b). The strong correlation between DTH and both TNF-α and IFN-γ responses in the present study indicates the importance of the DTH response as an early marker of the outcome of a vaccination study.…”

“…The development of a safe vaccine may provide an immunological control strategy. There is no available vaccine for the control of leishmaniasis to date (MUTISO et al, 2010b). It is apparent that an effective Leishmania vaccine will only be achieved by careful selection of both an appropriate adjuvant as well as an antigen (MUTISO et al, 2010a).…”

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

“…major, along with Montanide ISA 720 (MISA) adjuvant, has been reported to be an effective antigen candidate against murine cutaneous leishmaniasis [10].…”

Old World cutaneous leishmaniasis: diagnosis and treatment

“…The results indicated that volunteers who developed CL in the vaccine arm showed a slightly higher in vitro proliferative response than cases who received BCG alone. 60 Vaccination of C57BL/6 mice with live Leishmania major plus CpG DNA (Lm/CpG) prevents lesion development and provides long-term immunity.…”