Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis

The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL). Epitope-based immuno...

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Published in:PloS one 2014-10, Vol.9 (10), p.e110014-e110014
Main Authors: Costa, Lourena Emanuele, Goulart, Luiz Ricardo, Pereira, Nathália Cristina de Jesus, Lima, Mayara Ingrid Sousa, Duarte, Mariana Costa, Martins, Vivian Tamietti, Lage, Paula Sousa, Menezes-Souza, Daniel, Ribeiro, Tatiana Gomes, Melo, Maria Norma, Fernandes, Ana Paula, Soto, Manuel, Tavares, Carlos Alberto Pereira, Chávez-Fumagalli, Miguel Angel, Coelho, Eduardo Antonio Ferraz
Format: Article
Language:English
Subjects:
Analysis
Animal models
Animals
Antibodies
Antigenic determinants
Antigens
Antigens, Protozoan - immunology
Biology and Life Sciences
Bone marrow
CD8 antigen
Cloning
Cytokines
Disease Models, Animal
Display devices
Dogs
Epitopes
Formulations
Granulocyte-macrophage colony-stimulating factor
Granulocytes
Immune response
Immune system
Immunoglobulin G
Infections
Interleukin 10
Interleukin 12
Interleukin 4
Leishmania
Leishmania infantum
Leishmania infantum - immunology
Leishmania major
Leishmaniasis Vaccines - immunology
Leishmaniasis, Visceral - parasitology
Leishmaniasis, Visceral - prevention & control
Liver
Lymph nodes
Lymphocytes
Lymphocytes T
Medicine and Health Sciences
Mice
Parasitic diseases
Peptides
Phage display
Phages
Proteins
Spleen
Stimulation
Tropical diseases
Vaccination
Vaccines
Vector-borne diseases
Visceral leishmaniasis
γ-Interferon
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Summary:The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL). Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin), showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the parasite burden. This is the first study that describes phage-displayed peptides as successful immunogens in vaccine formulations against VL.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0110014