Investigation of Leish-111f Epitopes to Design a New Multi-epitope Vaccine Against Leishmania Major Using Immunoinformatics Approaches

BackgroundSince the incidence of various types of leishmaniasis, no definitive treatment has been considered for the disease, and due to its high prevalence worldwide, this issue has caused many concerns. Cutaneous leishmaniasis is the most common form of the disease which, can cause malignant lesions on the skin. Vaccination for the prevention and treatment of leishmaniasis can be the most effective way to combat this disease. In this study, we designed a new multi-epitope vaccine using immunoinformatics tools, which confirmed its effectiveness in the in silico.MethodsSequences Leish-111f protein (TSA, Leif, and LMSTI1) of Leishmania major (L. major) were downloaded from GenBank and with the help of immunoinformatic tools, was designed a new multi-epitope vaccine antigen of L. major.ResultTh and Tc epitopes of the leish-111f protein were predicted using bioinformatics tools. The final multi epitope was consisted of 18 CTL epitopes that joined by AAY linker. There are also 9 HTL epitopes in the structure of the final vaccine that were joined by GPGPG linker. The profilin adjuvant was also added into the construct by AAY Linker. There were 613 residues in the structure of the final construct. The multi epitope was stable and non-allergic. the data obtained from the binding of final multi-epitope vaccine-TLR11 residues (band lengths and weighted scores) showed that the ligand and the receptor have a high affinity to bind to each other. Moreover, in silico cloning approach, was improved the expression of proposed vaccine in E. coli host. Codon adaptation index and GC percent were calculated 1.0 and 53.35, respectivelyConclusionBased on these results, we hope that the multi-epitope vaccine, which contains the most appropriate epitopes of a strong Leishmania major immunogen, along with an adjuvant capable of binding to TLR11, will further stimulate the immune system against the L.major.

Migratory DCs activate TGF-β to precondition naïve CD8+ T cells for tissue-resident memory fate

Epithelial resident memory T (eTRM) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eTRM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8+ T cells and prepares them for the formation of eTRM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I–dependent interactions with peripheral tissue–derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β–activating αV integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.

Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice

Influenza is a persistent threat to public health. Here we report that double-layered peptide nanoparticles induced robust specific immunity and protected mice against heterosubtypic influenza A virus challenges. We fabricated the nanoparticles by desolvating a composite peptide of tandem copies of nucleoprotein epitopes into nanoparticles as cores and cross-linking another composite peptide of four tandem copies of influenza matrix protein 2 ectodomain epitopes to the core surfaces as a coating. Delivering the nanoparticles via dissolvable microneedle patch-based skin vaccination further enhanced the induced immunity. These peptide-only, layered nanoparticles demonstrated a strong antigen depot effect and migrated into spleens and draining (inguinal) lymph nodes for an extended period compared with soluble antigens. This increased antigen-presentation time correlated with the stronger immune responses in the nanoparticle-immunized group. The protection conferred by nanoparticle immunization was transferable by passive immune serum transfusion and depended partially on a functional IgG receptor FcγRIV. Using a conditional cell depletion, we found that CD8+ T cells were involved in the protection. The immunological potency and stability of the layered peptide nanoparticles indicate applications for other peptide-based vaccines and peptide drug delivery.