TY - JOUR
T1 - Immunogenicity and protective efficacy of a new Leishmania hypothetical protein applied as a DNA vaccine or in a recombinant form against Leishmania infantum infection
AU - Ribeiro, Patrícia A.F.
AU - Dias, Daniel S.
AU - Lage, Daniela P.
AU - Martins, Vívian T.
AU - Costa, Lourena E.
AU - Santos, Thaís T.O.
AU - Ramos, Fernanda F.
AU - Tavares, Grasiele S.V.
AU - Mendonça, Débora V.C.
AU - Ludolf, Fernanda
AU - Gomes, Dawidson A.
AU - Rodrigues, Michele A.
AU - Chávez-Fumagalli, Miguel A.
AU - Silva, Eduardo S.
AU - Galdino, Alexsandro S.
AU - Duarte, Mariana C.
AU - Roatt, Bruno M.
AU - Menezes-Souza, Daniel
AU - Teixeira, Antonio L.
AU - Coelho, Eduardo A.F.
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - DNA plasmid
KW - Hypothetical proteins
KW - Immune response
KW - Recombinant proteins
KW - Vaccine
KW - Visceral leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85059186392&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2018.12.025
DO - 10.1016/j.molimm.2018.12.025
M3 - Article
C2 - 30594673
AN - SCOPUS:85059186392
SN - 0161-5890
VL - 106
SP - 108
EP - 118
JO - Molecular Immunology
JF - Molecular Immunology
ER -