4.2 Article

Evaluation of protection induced by in vitro maturated BMDCs presenting CD8+ T cell stimulating peptides after a heterologous vaccination regimen in BALB/c model against Leishmania major

Journal

EXPERIMENTAL PARASITOLOGY
Volume 223, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.exppara.2021.108082

Keywords

Cutaneous leishmaniasis; Dendritic cell; DNA; Epitope; Vaccine

Categories

Funding

  1. Pasteur Institute of Iran [956]
  2. Iran National Science Foundation [97003540]

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The study found that the DC prime-DNA boost vaccine can induce Th1 polarization immune response, but its effectiveness in fighting infection is limited.
Leishmaniasis is a complex vector-borne disease mediated by Leishmania parasite and a strong and long-lasting CD4(+) Th1 and CD8(+)-T cell immunity is required to control the infection. Thus far multivalent subunit vaccines have met this requirement more promisingly. However several full protein sequences cannot be easily arranged in one construct. Instead, new emerging immune-informatics based epitope formulations surpass this restriction. Herein, we aimed to examine the protective potential of a dendritic cell based vaccine presenting epitopes to CD8(+) and CD4(+)-T cells in combination with DNA vaccine encoding the same epitopes against murine cutaneous leishmaniasis. Immature DCs were loaded with epitopes (selected from parasite proteome) in vitro with or without CpG oligonucleotides and were used to immunize BALB/c mice. Peptide coding DNA was used to boost the system and immunological responses were evaluated after Leishmania (L.) major infectious challenge. The pre-challenge response to included epitopes was Th1 polarized which potentially lowered the infection at early time points post-challenge but not at later weeks. Collectively, DC prime-DNA boost was found to be a promising approach for Th1 polarization however the constituent epitopes undoubtedly make a significant contribution in the protection outcome of the vaccine.

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