A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8+ T Cells Essential for the Protection against Experimental Visceral Leishmaniasis

Abstract

Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4+ TH1 and CD8+ T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L. infantum proteins (cysteine peptidase A, histone H1, and kinetoplastid membrane protein 11), in order to be encapsulated in poly(lactic-co-glycolic) acid nanoparticles with or without the adjuvant monophosphoryl lipid A (MPLA) or surface modification with an octapeptide targeting the tumor necrosis factor receptor II. We aimed to construct differentially functionalized peptide-based nanovaccine candidates and investigate their capacity to stimulate the immunomodulatory properties of dendritic cells (DCs), which are critical regulators of adaptive immunity generated upon vaccination. According to our results, DCs stimulation with the peptide-based nanovaccine candidates with MPLA incorporation or surface modification induced an enhanced maturation profile with prominent IL-12 production, promoting allogeneic T cell proliferation and intracellular production of IFNγ by CD4+ and CD8+ T cell subsets. In addition, DCs stimulated with the peptide-based nanovaccine candidate with MPLA incorporation exhibited a robust transcriptional activation, characterized by upregulated genes indicative of vaccine-driven DCs differentiation toward type 1 phenotype. Immunization of HLA A2.1 transgenic mice with this peptide-based nanovaccine candidate induced peptide-specific IFNγ-producing CD8+ T cells and conferred significant protection against L. infantum infection. Concluding, our findings supported that encapsulation of more than one chimeric multi-epitope peptides from different immunogenic L. infantum proteins in a proper biocompatible delivery system with the right adjuvant is considered as an improved promising approach for the development of a vaccine against VL.

Excavating SARS‐coronavirus 2 genome for epitope‐based subunit vaccine synthesis using immunoinformatics approach

“…Further, the PADRE sequence, composed of 13 amino acid residues—AKFVAAWTLKAAA—was also considered in the vaccine sequence. The PADRE sequence has affinity toward number of human and mouse HLA Class II alleles and induce the T‐helper responses (Athanasiou et al, 2017). An adjuvant β‐defensin was linked via EAAAK linker to the vaccine sequence to enhance its immunity.…”

Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB/c Mice

“…Based on the immunological findings in the spleen of Cockt-1 immunized mice, we assessed the parasite load in the endpoint to evaluate the efficacy of the peptide cocktails vaccine strategy. Regarding peptide vaccines for leishmaniasis, few studies are reported, and they are in immunogenicity phase with no outcome for parasite load [3][4][5]34,43,44]. Our results demonstrate that Cockt-1 can promote a significant reduction of parasite load in the spleen, which was not observed for Cockt-2.…”

Advancements in prophylactic and therapeutic nanovaccines

“…Stimulation with the peptide-based nanovaccine induced maturation of DCs and IL-12 production subsequently promoting allogeneic T cell proliferation and production of IFN-γ by CD4 + and CD8 + T cell. On immunization of transgenic mice with this peptide-based nanovaccine induced peptide-specific IFN-γ producing CD8 + T cells and conferred protection against L. infantum infection [130] . Multiple self-assembling peptide-based nanovaccines containing epitopes of Toxoplasma gondii specific antigens have been designed.…”