Recombinant guanosine-5--triphosphate (GTP)-binding protein associated with Poloxamer 407-based polymeric micelles protects against Leishmania infantum infection.
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2022
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Resumo
Leishmania virulence proteins should be considered as vaccine candidates against disease, since they are involved
in developing infection in mammalian hosts. In a previous study, a Leishmania guanosine-5′
-triphosphate (GTP)-
binding protein was identified as a potential parasite virulence factor. In the present work, the gene encoding
GTP was cloned and the recombinant protein (rGTP) was evaluated as a vaccine candidate against Leishmania
infantum infection. The protein was associated with saponin (rGTP/Sap) or Poloxamer 407-based micelles (rGTP/
Mic) as adjuvants, and protective efficacy was investigated in BALB/c mice after parasite challenge. Both rGTP/
Sap and rGTP/Mic compositions induced a Th1-type immune response in vaccinated animals, with significantly
higher levels of IFN-γ, IL-12, IL-2, TNF-α, GM-CSF, nitrite, specific IgG2a isotype antibody and positive lym-
phoproliferation, when compared to the control groups. This response was accompanied by significantly lower
parasite load in the spleens, livers, bone marrows and draining lymph nodes of the animals. Immunological and
parasitological evaluations indicated that rGTP/Mic induced a more polarized Th1-type response and higher
reduction in the organ parasitism, and with lower hepatotoxicity, when compared to the use of rGTP/Sap. In
conclusion, our preliminary data suggest that rGTP could be considered for further development as a vaccine
candidate to protect against VL.
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Micelle, Saponin, Immune response, Vaccine, Visceral leishmaniasis
Citação
LAGE, D. P. et al. Recombinant guanosine-5--triphosphate (GTP)-binding protein associated with Poloxamer 407-based polymeric micelles protects against Leishmania infantum infection. Cytokine, v. 153, p. 155865-155877, 2022. Disponível em: <https://www.sciencedirect.com/science/article/pii/S1043466622000746?via%3Dihub>. Acesso em: 11 out. 2022.