The association between rLiHyp1 protein plus adjuvant and amphotericin B is an effective immunotherapy against visceral leishmaniasis in mice

Daniela P. Lage, Vívian T. Martins, Danniele L. Vale, Camila S. Freitas, Breno L. Pimenta, Gabriel J.L. Moreira, Fernanda F. Ramos, Isabela A.G. Pereira, Raquel S. Bandeira, Marcelo M. de Jesus, Fernanda Ludolf, Grasiele S.V. Tavares, Miguel A. Chávez-Fumagalli, Bruno M. Roatt, Myron Christodoulides, Eduardo A.F. Coelho

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Resumen

Treatment of visceral leishmaniasis (VL) is compromised by drug toxicity, high cost and/or the emergence of resistant strains. Though canine vaccines are available, there are no licensed prophylactic human vaccines. One strategy to improve clinical outcome for infected patients is immunotherapy, which associates a chemotherapy that acts directly to reduce parasitism and the administration of an immunogen-adjuvant that activates the host protective Th1-type immune response. In this study, we evaluated an immunotherapy protocol in a murine model by combining recombinant (r)LiHyp1 (a hypothetical amastigote-specific Leishmania protein protective against Leishmania infantum infection), with monophosphoryl-lipid A (MPLA) as adjuvant and amphotericin B (AmpB) as reference antileishmanial drug. We used this protocol to treat L. infantum infected-BALB/c mice, and parasitological, immunological and toxicological evaluations were performed at 1 and 30 days after treatment. Results showed that mice treated with rLiHyp1/MPLA/AmpB presented the lowest parasite burden in all organs evaluated, when both a limiting dilution technique and qPCR were used. In addition, these animals produced higher levels of IFN-γ and IL-12 cytokines and IgG2a isotype antibody, which were associated with lower production of IL-4 and IL-10 and IgG1 isotype. Furthermore, low levels of renal and hepatic damage markers were found in animals treated with rLiHyp1/MPLA/AmpB possibly reflecting the lower parasite load, as compared to the other groups. We conclude that the rLiHyp1/MPLA/AmpB combination could be considered in future studies as an immunotherapy protocol to treat against VL.

Idioma originalInglés
Número de artículo106986
PublicaciónActa Tropica
Volumen246
DOI
EstadoPublicada - oct. 2023

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