Authors:
Stober, C. B.; Jeronimo, S. M. B.; Pontes, N. N.; Miller, E. N.; Blackwell, J. M.
Keywords:
Visceral leishmaniasis (VL), CD4-derived interferon-γ (IFN-γ), interleukin-10 (IL-10), vaccine, tumor necrosis factor-α (TNF-α), immune responses, Leishmania infantum chagasi, Brazil
Abstract
Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process.
We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania -specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts.
Magnitude of DTH correlated with crude Leishmania antigen-driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients.
The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36-71% of responders) in recovered VL patients and DTH+ persons.
This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.