Immunogenicity and protective efficacy of a new Leishmania hypothetical protein applied as a DNA vaccine or in a recombinant form against Leishmania infantum infection

• Published in: Molecular immunology Vol. 106; pp. 108 - 118
• Main Authors: Ribeiro, Patrícia A.F., Dias, Daniel S., Lage, Daniela P., Martins, Vívian T., Costa, Lourena E., Santos, Thaís T.O., Ramos, Fernanda F., Tavares, Grasiele S.V., Mendonça, Débora V.C., Ludolf, Fernanda, Gomes, Dawidson A., Rodrigues, Michele A., Chávez-Fumagalli, Miguel A., Silva, Eduardo S., Galdino, Alexsandro S., Duarte, Mariana C., Roatt, Bruno M., Menezes-Souza, Daniel, Teixeira, Antonio L., Coelho, Eduardo A.F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2019
• Subjects: Adult; Animals; Antibodies, Protozoan - immunology; Cytokines - immunology; DNA plasmid; Female; Humans; Hypothetical proteins; Immune response; Immunogenicity, Vaccine; Immunoglobulin G - immunology; Leishmania infantum - immunology; Leishmaniasis Vaccines - immunology; Leishmaniasis Vaccines - pharmacology; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - prevention & control; Male; Mice; Mice, Inbred BALB C; Middle Aged; Protozoan Proteins - immunology; Recombinant proteins; Vaccine; Vaccines, DNA - immunology; Vaccines, DNA - pharmacology; Visceral leishmaniasis; Vaccine; Hypothetical proteins; Immune response; Visceral leishmaniasis; Recombinant proteins; DNA plasmid
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2018.12.025

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•A Leishmania hypothetical protein, LiHyP, was evaluated as a vaccine candidate in mice.•It was administered as a recombinant protein plus saponin or in a DNA plasmid.•Both immunization strategies induced Th1 response in the vaccinated animals.•DNA LiHyP and rLiHyP/saponin induced partial protection in L. infantum-infected mice.•LiHyP was immunogenic in human PBMC from healthy subjects and VL patients.
Vaccination is one the most important strategies for the prevention of visceral leishmaniasis (VL). In the current study, a new Leishmania hypothetical protein, LiHyP, which was previously showed as antigenic in an immunoproteomic search in canine VL, was evaluated regarding its immunogenicity and protective efficacy against Leishmania infantum infection. The effects of the immunization using LiHyP were evaluated when administered as a DNA plasmid (DNA LiHyP) or recombinant protein (rLiHyP) associated with saponin. The immunity elicited by both vaccination regimens reduced the parasitism in liver, spleen, bone marrow and draining lymph nodes, being associated with high levels of IFN-γ, IL-12, GM-CSF, and specific IgG2a antibody, besides low production of IL-4, IL-10, and protein and parasite-specific IgG1 antibodies. CD4+ T cells contributed more significantly to IFN-γ production in the rLiHyP/saponin group, while CD8+ T cells were more important in the production of this cytokine in the DNA LiHyP group. In addition, increased IFN-γ secretion, along with low levels of IL-10, were found when PBMCs from treated VL subject and healthy individuals were stimulated with the recombinant protein. In conclusion, when administered either as a DNA plasmid or recombinant protein, LiHyP can direct the immune response towards a Th1 immune profile, protecting animals against L. infantum infection; therefore, it can be seen as a promising immunogen against human VL.