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 T-cell 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.

Trichuris trichiura是一种寄生虫，全球感染5亿人，导致结肠炎，生长迟缓和Trichuris痢疾综合症。没有可用于预防Trichuris感染的许可疫苗，目前的治疗效果有限。chu虫感染与贫穷有关，降低了儿童的教育成绩和成年人的经济生产力。我们基于选择的T细胞表位掺入病毒样颗粒的基础上，采用了系统的，多阶段的过程来鉴定候选抗滴虫病的疫苗。我们进行了系统的审查，以确定最合适的计算机预测工具来预测组织相容性复杂的II类（MHC-II）分子T细胞表位。这些工具用于从Trichuris基因组的预测ORF中鉴定候选MHC-II表位，并使用纳入和排除标准进行选择。将选定的表位掺入乙型肝炎核心抗原病毒样颗粒（VLP）。骨髓来源的树突状细胞和骨髓来源的巨噬细胞在体外对VLP有反应，而不管VLP是否还包括T细胞表位。VLP被内化并共定位在抗原呈递细胞溶酶体中。攻击感染后，接种了VLPs + T细胞表位的小鼠表现出明显减轻的蠕虫负担，并安装了Trichuris特异性IgM和IgG2c抗体反应。VLPs + T细胞表位对小鼠的保护以肠系膜淋巴结（MLN）衍生的Th2细胞因子的产生和杯状细胞增生为特征。总体而言，我们的数据表明，基于计算机基因组的CD4 + T细胞表位预测与VLP递送相结合，为开发有效，安全和负担得起的蠕虫疫苗提供了有希望的途径。