Identification of Immunodominant Antigens From a First-Generation Vaccine Against Cutaneous Leishmaniasis
Leishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against and to identify its immunodominant anti...
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Published in | Frontiers in immunology Vol. 13; p. 825007 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
12.05.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Leishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the
genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against
and to identify its immunodominant antigens. BALB/c mice were inoculated with phosphate buffer sodium (PBS), total
antigens (TLAs), or TLA with Poly (I:C) and Montanide ISA 763. The humoral and cellular immune response was evaluated before infection. IgG, IgG1, and IgG2a were measured on serum, and IFN-γ, IL-4, and IL-10 cytokines as well as cell proliferation were measured on a splenocyte culture from vaccinated mice. Immunized mice were challenged with 10
infective parasites of
on the footpad. After infection, the protection provided by the vaccine was analyzed by measuring lesion size, splenic index, and parasite load on the footpad and spleen. To identify immunodominant antigens, total proteins of
were separated on 2D electrophoresis gel and transferred to a membrane that was incubated with serum from immunoprotected mice. The antigens recognized by the serum were analyzed through a mass spectrometric assay (LC-MS/MS-IT-TOF) to identify their protein sequence, which was subjected to bioinformatic analysis. The first-generation vaccine induced higher levels of antibodies, cytokines, and cell proliferation than the controls after the second dose. Mice vaccinated with TLA + Poly (I:C) + Montanide ISA 763 showed less footpad swelling, a lower splenic index, and a lower parasite load than the control groups (PBS and TLA). Four immunodominant proteins were identified by mass spectrometry: cytosolic tryparedoxin peroxidase, an uncharacterized protein, a kinetoplast-associated protein-like protein, and a putative heat-shock protein DNAJ. The identified proteins showed high levels of conserved sequence among species belonging to the
genus and the Trypanosomatidae family. These proteins also proved to be phylogenetically divergent to human and canine proteins. TLA + Poly (I:C) + Montanide ISA 763 could be used as a first-generation vaccine against leishmaniasis. The four proteins identified from the whole-protein vaccine could be good antigen candidates to develop a new-generation vaccine against leishmaniasis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Irene S. Soares, University of São Paulo, Brazil This article was submitted to Parasite Immunology, a section of the journal Frontiers in Immunology Reviewed by: Celio Geraldo Freire-de-Lima, Federal University of Rio de Janeiro, Brazil; Debora Decote-Ricardo, Universidade Federal Rural do Rio de Janeiro, Brazil; Danilo Ciccone Miguel, State University of Campinas, Brazil These authors have contributed equally to this work and share last authorship |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.825007 |