Details

Autor(en) / Beteiligte

• Oliveira-da-Silva, João A.
• Machado, Amanda S.
• Ramos, Fernanda F.
• Tavares, Grasiele S.V.
• Lage, Daniela P.
• Mendonça, Débora V.C.
• Pereira, Isabela A.G.
• Santos, Thaís T.O.
• Martins, Vívian T.
• Carvalho, Lívia M.
• Freitas, Camila S.
• Ludolf, Fernanda
• Reis, Thiago A.R.
• Bandeira, Raquel S.
• Silva, Alessandra M.
• Costa, Lourena E.
• Oliveira, Jamil S.
• Duarte, Mariana C.
• Roatt, Bruno M.
• Teixeira, Antônio L.
• Coelho, Eduardo A.F.

Titel

A Leishmania amastigote-specific hypothetical protein evaluated as recombinant protein plus Th1 adjuvant or DNA plasmid-based vaccine to protect against visceral leishmaniasis

Ist Teil von

• Cellular immunology, 2020-10, Vol.356, p.104194-104194, Article 104194

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •A Leishmania amastigote-specific protein was evaluated as vaccine against VL.•The protein was administered as a recombinant antigen or as DNA vaccine.•Mice receiving both immunization schedules mounted a Th1-type response.•Significant reductions in the parasite load were found in all evaluated organs.•LiHyJ was immunogenic in PBMCs from treated patients and healthy subjects. Most studies evaluating vaccine candidates against visceral leishmaniasis (VL) have used parasite promastigote-expressed antigens; however, Leishmania proteins expressed in the amastigote forms should be considered, since few hours after infection this stage comes into contact with the host immune system and is responsible for the development of the disease. In this context, in the present study, a Leishmania amastigote-specific hypothetical protein, called LiHyJ, was evaluated as a recombinant protein plus saponin as an adjuvant or DNA vaccine to protect against VL. The vaccine effect was evaluated by means of the evaluation of immunological and parasitological analyses performed in BALB/c mice against Leishmania infantum infection. Results showed that rLiHyJ/saponin and DNA LiHyJ induced significantly higher levels of anti-protein and anti-parasite IFN-γ, IL-12, GM-CSF, and IgG2a isotype antibodies, which were associated with a low presence of IL-4 and IL-10. DNA vaccination induced higher IFN-γ production, mainly by CD8+ T cells, while rLiHyJ/saponin stimulated the production of this cytokine, mainly by CD4+ T cells. The parasite load evaluated in distinct organs showed that both immunization schedules significantly reduced organic parasitism, when compared to the controls. Similar results were found in the immunological and parasitological assays when using the recombinant protein or DNA, although the vaccination with rLiHyJ plus saponin induced a slightly higher Th1 response and lower parasite load, when compared to the use of DNA plasmid. The protein also proved to be immunogenic when peripheral blood mononuclear cells of treated VL patients and healthy subjects were in vitro stimulated, since higher IFN-γ and lower IL-4 and IL-10 levels were found in the culture supernatants. In conclusion, LiHyJ should be considered in future studies as a vaccine candidate to protect against VL.