1. Leishmania infantum pyridoxal kinase evaluated in a recombinant protein and DNA vaccine to protects against visceral leishmaniasis
- Author
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Raquel S. Bandeira, Jamil S. Oliveira, Daniela P. Lage, Camila Stefanie Fonseca de Oliveira, Amanda S. Machado, Alessandra M. Silva, Fernanda Ludolf, Antônio Lúcio Teixeira, Fernanda F. Ramos, Isabela A.G. Pereira, Daniel Menezes-Souza, Bruno Mendes Roatt, Débora V.C. Mendonça, Lourena E. Costa, Mariana C. Duarte, Grasiele S.V. Tavares, Thiago A.R. Reis, Lívia M. Carvalho, Eduardo A.F. Coelho, Thaís T.O. Santos, Vívian T. Martins, and João A. Oliveira-da-Silva more...
- Subjects
0301 basic medicine ,Antigenicity ,Immunogen ,Immunology ,Antibodies, Protozoan ,Antigens, Protozoan ,DNA vaccination ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,medicine ,Vaccines, DNA ,Animals ,Humans ,Leishmania infantum ,Pyridoxal Kinase ,Molecular Biology ,Leishmaniasis Vaccines ,biology ,Immunogenicity ,medicine.disease ,biology.organism_classification ,Virology ,Recombinant Proteins ,030104 developmental biology ,Visceral leishmaniasis ,biology.protein ,Leishmaniasis, Visceral ,Antibody ,030215 immunology - Abstract
Leishmania infantum pyridoxal kinase (PK) protein was characterized after an immunoproteomics screening performed with the sera from patients suffering visceral leishmaniasis (VL). Since it was recognized by sera of mammalian hosts infected by a viscerotropic Leishmania species, PK could emerge as a new vaccine candidate against disease, due to its antigenicity and immunogenicity. In this context, in the present study, the effects of the immunization using PK were evaluated when administered as a DNA plasmid (pDNAA3/PK) or recombinant protein (rPK) plus saponin. The immune response elicited by both vaccination regimens reduced in significant levels the parasite load in spleen, liver, draining lymph nodes and bone marrow, being associated with the development of Th1-type immune response, which was characterized by 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. CD8+ T cells were more important in the IFN-γ production in the pDNAA3/PK group, while CD4+ T cells contributed more significantly to production of this cytokine in the rPK/Saponin group. In addition, increased IFN-γ secretion, along with low levels of IL-10, were found when PBMCs from VL patients after treatment and healthy individuals were stimulated with the protein. In conclusion, when administered either as a DNA plasmid or recombinant protein plus adjuvant, PK can direct the immune response towards a Th1-type immune profile, protecting mice against L. infantum challenge; therefore, it can be seen as a promising immunogen against human VL. more...
- Published
- 2020