In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection

Abstract

Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children's educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T-cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule Tcell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T-cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.

Epitope-Based Potential Vaccine Candidate for Humoral and Cell-Mediated Immunity to Combat Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic

“… 28 , 29 There are evidence which supports that in silco predictions are helpful in successful production of commercially important vaccines. 30 However, the structural modifications, delivery systems, and adjuvants are the additional requirements in the formulation because of low immunogenicity caused by their structural complexity and low molecular weight. 31 Recently, a set of B and T cell epitopes from the highly conserved region in SARS-CoV-2 were identified, which may help in developing vaccine candidates.…”

Bioinformatic HLA Studies in the Context of SARS-CoV-2 Pandemic and Review on Association of HLA Alleles with Preexisting Medical Conditions

“…Among MHC II epitope prediction datasets, such as SMM-align, ProPred, NetMHCIIpan, and RANKPEP, ProPred predicts MHC II epitopes based on a quantitative matrix and TEPITOPE methods with high accuracy of its position-specific scoring matrix (PSSM), which is trained by the data from empirical experiments [ 64 ]. The prediction of only HLA-DR epitopes is the major drawback of this database [ 65 ]. Another top tool is SMM-align that utilizes the IEBD server for MHC II binding predictions based on quantitative matrices [ 64 ].…”

“…SMM-align performs the prediction of peptide : MHC binding affinities based on pan-specific receptors even with very restricted binding data; also, this method contains the data related to the peptide flanking residues (PFRs) on either side of the binding core sequences, improving the stability of the binding as well as its prediction [ 66 ]. The RANKPEP tool, like NetMHCIIpan, can predict MHC II binding affinities of HLA-DR, DQ, and DP through the PSSM method based on peptide sequence alignments, but its sensitivity is lower than the two former databases [ 62 , 65 , 67 ].…”

T Cell Specificity: A Great Challenge in Chagas Disease

“…The specific responses of both types of T cells depend on the processing and presentation of T. cruzi peptides by antigen presenting cells (APC) and their recognition by the T cell receptor (TCR). For this reason, studies on new therapeutic approaches (12)(13)(14)(15) attempt to understand the mechanisms underlying the interaction between peptide-MHC (pMHC, MHC: major histocompatibility complex) complexes and TCR, and also functional and phenotypic characteristics of antigenspecific T cells, which can be investigated by diverse strategies (16)(17)(18)(19)(20)(21)(22)(23). In Chagas disease, different T. cruzi targets that can be processed and presented to T cells have been evaluated.…”