TY - JOUR
T1 - 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
AU - Ramos, Fernanda Fonseca
AU - Costa, Lourena Emanuele
AU - Dias, Daniel Silva
AU - Santos, Thaís Teodoro Oliveira
AU - Rodrigues, Marcella Rezende
AU - Lage, Daniela Pagliara
AU - Salles, Beatriz Cristina Silveira
AU - Martins, Vívian Tamietti
AU - Ribeiro, Patrícia Aparecida Fernandes
AU - Chávez-Fumagalli, Miguel Angel
AU - Dias, Ana Carolina Silva
AU - Alves, Patrícia Terra
AU - Vieira, Érica Leandro Marciano
AU - Roatt, Bruno Mendes
AU - Menezes-Souza, Daniel
AU - Duarte, Mariana Costa
AU - Teixeira, Antonio Lúcio
AU - Goulart, Luiz Ricardo
AU - Coelho, Eduardo Antonio Ferraz
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/21
Y1 - 2017/12/21
N2 - 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.
AB - 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.
KW - Antibodies
KW - Immune response
KW - Peripheral blood mononuclear cells
KW - Phage display
KW - Vaccine
KW - Visceral leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85039039498&partnerID=8YFLogxK
U2 - 10.1186/s13071-017-2576-8
DO - 10.1186/s13071-017-2576-8
M3 - Article
C2 - 29268793
AN - SCOPUS:85039039498
SN - 1756-3305
VL - 10
JO - Parasites and Vectors
JF - Parasites and Vectors
IS - 1
M1 - 617
ER -