Understanding the importance of vaccine formulation in generating protective immune responses against Leishmania amazonensis challenge

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Abstract

Leishmaniasis presents with a broad range of clinical manifestations and is caused by infection with Leishmania parasites. The life-long immunity found in individuals who naturally healed their infections suggests that development of a vaccine in feasible, although there is not one yet approved for human use. The immune responses in murine models are well characterized, and suggest possible correlates of protection induced by vaccination. However, these immune responses were determined by the prototypical species L. major, and are not necessarily found in all Leishmania infections. Therefore, we are working towards understanding the correlates of vaccine-mediated protection in L. amazonensis, which is required for properly determining protective mechanisms. We tested both conventional and unorthodox vaccine regimens, but were not able to recapitulate the correlates of protection determined by L. major. Conversely, we found IFNγ-producing CD8+ T cells correlated with protection, while ineffective vaccines induced a mixed Th1/Th2 immune response. These data can help to establish parameters for determing vaccine efficacy in L. amazonensis.

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Leishmania, vaccine, TLR4, TLR9, adjuvant
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