Selection strategy of phage-displayed immunogens based on an in vitro evaluation of the Th1 response of PBMCs and their potential use as a vaccine against Leishmania infantum infection

Fernanda Fonseca Ramos, Lourena Emanuele Costa, Daniel Silva Dias, Thaís Teodoro Oliveira Santos, Marcella Rezende Rodrigues, Daniela Pagliara Lage, Beatriz Cristina Silveira Salles, Vívian Tamietti Martins, Patrícia Aparecida Fernandes Ribeiro, Miguel Angel Chávez-Fumagalli, Ana Carolina Silva Dias, Patrícia Terra Alves, Érica Leandro Marciano Vieira, Bruno Mendes Roatt, Daniel Menezes-Souza, Mariana Costa Duarte, Antonio Lúcio Teixeira, Luiz Ricardo Goulart, Eduardo Antonio Ferraz Coelho

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15 Citas (Scopus)

Resumen

Background: The development of a vaccine for the prevention of visceral leishmaniasis (VL) still represents a significant unmet medical need. A human vaccine can be found if one takes into consideration that many people living in endemic areas of disease are infected but do not develop active VL, including those subjects with subclinical or asymptomatic infection. Methods: In this study, a phage display was used to select phage-exposed peptides that were specific to immunoglobulin G (IgG) antibodies from asymptomatic and symptomatic VL patients, separating them from non-infected subjects. Phage clones presenting valid peptide sequences were selected and used as stimuli of peripheral blood mononuclear cells (PBMCs) obtained from both patients' groups and controls. Those with higher interferon-gamma (IFN-γ)/interleukin (IL)-10 ratios were further selected for vaccination tests. Results: Among 17 evaluated clones, two were selected, B1 and D11, and used to immunize BALB/c mice in an attempt to further validate their in vivo protective efficacy against Leishmania infantum infection. Both clones induced partial protection against the parasite challenge, which was evidenced by the reduction of parasitism in the evaluated organs, a process mediated by a specific T helper (Th)1 immune response. Conclusions: To the best of our knowledge, this study is the first to use a rational strategy based on in vitro stimulation of human PBMCs with selected phage-displayed clones to obtain new immunogens against VL.

Idioma originalInglés
Número de artículo617
PublicaciónParasites and Vectors
Volumen10
N.º1
DOI
EstadoPublicada - 21 dic. 2017
Publicado de forma externa

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