Open AccessIdentification of BALB/c Immune Markers Correlated with a Partial Protection to Leishmania infantum after Vaccination with a Rationally Designed Multi-epitope Cysteine Protease A Peptide-Based Nanovaccine
Author(s) -
Maria Agallou,
Maritsa Margaroni,
Evangelia Athanasiou,
Dimitra K. Toubanaki,
Katerina Kontonikola,
Konstantina Karidi,
Olga Kammona,
Costas Kiparissides,
Evdokia Karagouni
Publication year - 2017
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0005311
Subject(s) - plga , leishmania infantum , adjuvant , immunogenicity , immune system , epitope , balb/c , antigen , biology , leishmania , chemistry , microbiology and biotechnology , immunology , visceral leishmaniasis , biochemistry , leishmaniasis , in vitro , parasite hosting , world wide web , computer science
Background Through their increased potential to be engaged and processed by dendritic cells (DCs), nanovaccines consisting of Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with both antigenic moieties and adjuvants are attractive candidates for triggering specific defense mechanisms against intracellular pathogens. The aim of the present study was to evaluate the immunogenicity and prophylactic potential of a rationally designed multi-epitope peptide of Leishmania Cysteine Protease A (CPA 160-189 ) co-encapsulated with Monophosphoryl lipid A (MPLA) in PLGA NPs against L . infantum in BALB/c mice and identify immune markers correlated with protective responses. Methodology/Principal Findings The DCs phenotypic and functional features exposed to soluble (CPA 160-189 , CPA 160-189 +MPLA) or encapsulated in PLGA NPs forms of peptide and adjuvant (PLGA-MPLA, PLGA-CPA 160-189 , PLGA-CPA 160-189 +MPLA) was firstly determined using BALB/c bone marrow-derived DCs. The most potent signatures of DCs maturation were obtained with the PLGA-CPA 160-189 +MPLA NPs. Subcutaneous administration of PLGA-CPA 160-189 +MPLA NPs in BALB/c mice induced specific anti-CPA 160-189 cellular and humoral immune responses characterized by T cells producing high amounts of IL-2, IFN-γ and TNFα and IgG1/IgG2a antibodies. When these mice were challenged with 2x10 7 stationary phase L . infantum promastigotes, they displayed significant reduced hepatic (48%) and splenic (90%) parasite load at 1 month post-challenge. This protective phenotype was accompanied by a strong spleen lymphoproliferative response and high levels of IL-2, IFN-γ and TNFα versus low IL-4 and IL-10 secretion. Although, at 4 months post-challenge, the reduced parasite load was preserved in the liver (61%), an increase was detected in the spleen (30%), indicating a partial vaccine-induced protection. Conclusions/Significance This study provide a basis for the development of peptide-based nanovaccines against leishmaniasis, since it reveals that vaccination with well-defined Leishmania MHC-restricted epitopes extracted from various immunogenic proteins co-encapsulated with the proper adjuvant or/and phlebotomine fly saliva multi-epitope peptides into clinically compatible PLGA NPs could be a promising approach for the induction of a strong and sustainable protective immunity.