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Disordered epitopes as peptide vaccines.

ABSTRACT: The development of clinically useful peptide-based vaccines remains a long-standing goal. This review highlights that intrinsically disordered protein antigens, which lack an ordered three-dimensional structure, represent excellent starting points for the development of such vaccines. Disordered proteins represent an important class of antigen in a wide range of human pathogens, and, contrary to widespread belief, they are frequently targets of protective antibody responses. Importantly, disordered epitopes appear invariably to be linear epitopes, rendering them ideally suited to incorporation into a peptide vaccine. Nonetheless, the conformational properties of disordered antigens, and hence their recognition by antibodies, frequently depend on the interactions they make and the context in which they are presented to the immune system. These effects must be considered in the design of an effective vaccine. Here we discuss these issues and propose design principles that may facilitate the development of peptide vaccines targeting disordered antigens.

SUBMITTER: MacRaild CA

PROVIDER: S-EPMC7167742 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Disordered epitopes as peptide vaccines.

MacRaild Christopher A CA Seow Jeffrey J Das Sreedam C SC Norton Raymond S RS

Peptide science (Hoboken, N.J.) 20180414 3

The development of clinically useful peptide-based vaccines remains a long-standing goal. This review highlights that intrinsically disordered protein antigens, which lack an ordered three-dimensional structure, represent excellent starting points for the development of such vaccines. Disordered proteins represent an important class of antigen in a wide range of human pathogens, and, contrary to widespread belief, they are frequently targets of protective antibody responses. Importantly, disorde ...[more]

PMID: 32328540

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Project description:Recent outbreak of 2019 novel Corona virus poses serious challenge for the global health system. In lieu of paucity of experimental data, tools and the very basic understanding of host immune responses against SARS-CoV-2, well thought effective measures are needed to control COVID-19 pandemic. We have identified specific overlapping antigenic peptide epitopes (OAPE) within the 4 structural proteins of SARS-CoV-2 predictive of triggering robust CD4 and CD8 T cell responses in host using bio-informatics tools (NetMHC4.0, IEDB, and Vaxijen2.0). We speculate an early release of pro-inflammatory cytokines for protection and later release of anti-inflammatory cytokines for prevention of immunopathology in designing a vaccine for Covid-19. Therefore, the selected immunogenic OAPE were subjected to in silico tools (IL-6-Pred, IFNepitope and PIP-EL) for analyzing their pro-inflammatory response. The OAPEs found to be pro-inflammatory in nature were further subjected to prediction servers (IL-4-Pred, IL-10-Pred, Pre-AIP) to characterize them as inducers of anti-inflammatory response as well. We finally filtered out 12 OAPE which had affinity for both CD4 and CD8 T cells as well as were inducers of pro-inflammatory and anti-inflammatory cytokines. On confirmation of OAPE binding affinity for respective T cell specific MHC allele using docking studies (pepATTRACT, Hex8.0 and Discovery studio) they were found to be have more immunogenic potential than the 3 negative control peptides (NCPs) included in the study. Additionally, we constructed CTxB-adjuvanated multi-epitopic vaccine inclusive of the 12 OAPEs which was non-toxic, non-allergenic and capable of inducing both pro-inflammatory and anti-inflammatory cytokines. A successful in silico cloning and docking of modeled subunit vaccine construct with toll like receptor-2 (TLR-2) confirmed the high efficacy of our multi-epitopic vaccine which can through a balanced interplay of cytokines help in creating a steady-state immune equilibrium. In silico immune simulation studies with the vaccine using C-ImmSim server also showed higher percentage of T cells along with production of pro-inflammatory as well as some anti-inflammatory cytokines. Experimental validation of this prediction based study on Peripheral Blood Mononuclear Cells (PBMCs) of un-infected individuals, patients and recovered individuals will facilitate production of high priority effective SARS -CoV-2 vaccine candidate.Supplementary informationThe online version contains supplementary material available at 10.1007/s40203-021-00098-7.

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Disordered epitopes as peptide vaccines.

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Disordered epitopes as peptide vaccines.

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