A specific Leishmania infantum polyepitope vaccine triggers Th1-type immune response and protects against experimental visceral leishmaniasis.
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2022
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The development of an immunogenic, effective, and safe vaccine is essential as an alternative for disease control.
The present study aimed to evaluate the immunogenicity and efficacy potential of a polyepitope T-cell antigen
candidate against visceral leishmaniasis in a murine model. BALB/c mice were immunized with three doses
subcutaneously with Poly-T Leish alone or adjuvanted with Saponin plus Monophosphoryl lipid A, with 15-day
intervals between doses, and challenged with 107 stationary-phase Leishmania infantum promastigotes via tail
vein. Immunogenicity and parasitism in spleen and liver of immunized mice were evaluated 45 days postchallenge. Our results revealed that the immunization with Poly-T Leish and Poly-T Leish/SM increases the
percentage of specific T (CD4+ and CD8+) lymphocytes proliferation in vitro after antigen-specific stimulation.
Also, Poly-T Leish and Poly-T Leish/SM groups showed a high percentage of IFN-γ and TNF-α-producing T cells,
meanwhile, the Poly-T Leish/SM group also showed an increased percentage of multifunctional T cells producing
double and triple-positive (IFN-γ+TNF-α+IL-2+) cytokines. The immunization with Poly-T Leish or Poly-T Leish/
SM stimulated a decreased IL-4 and IL-10 compared to the Saline and adjuvant group. Poly-T Leish/SM
immunized mice exhibit a noteworthy reduction in the parasite burden (spleen and liver) through real-time PCR
(96%). Moreover, we observed higher nitrite secretion in 120-hour stimulated-culture supernatant using Griess
method. We demonstrated that the Poly-T Leish/SM candidate was potentially immunogenic, providing
enhancement of protective immune mechanisms, and conferred protection reducing parasitism. Our candidate
was considered potential against visceral leishmaniasis, and eventually, could be tested in phase I and II clinical
trials in dogs.
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Visceral leishmaniasis, Leishmania infantum, Protozoan proteins, Polyepitope vaccine, Immunogenicity
Citação
OSTOLIN, T. L. V. D. P. et al. A specific Leishmania infantum polyepitope vaccine triggers Th1-type immune response and protects against experimental visceral leishmaniasis. Cellular Immunology, v. 380, artigo 104592, out. 2022. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0008874922001174?via%3Dihub>. Acesso em: 01 ago. 2023.