Rangel Giselle, Bárcena Juan, Moreno Noelia, Mata Carlos P, Castón José R, Alejo Alí, Blanco Esther
Centro de Investigación en Sanidad Animal (CISA, CSIC-INIA), Valdeolmos, 28130 Madrid, Spain.
Department of Structure of Macromolecules, Centro Nacional de Biotecnología/CSIC, Cantoblanco, 28049 Madrid, Spain.
Vaccines (Basel). 2021 May 7;9(5):470. doi: 10.3390/vaccines9050470.
Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140-158)) and a T-cell epitope [3A (21-35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.
目前,将病毒样颗粒(VLPs)确立为疫苗开发的有力工具存在明显趋势。VLPs是可调节的纳米颗粒,可设计用作外源抗原多聚体展示的平台。我们之前报道过,源自兔出血症病毒(RHDV)的VLPs构成了一种出色的疫苗载体,能够诱导针对插入的异源T细胞毒性和B细胞表位的特异性保护性免疫反应。在此,我们评估嵌合RHDV VLPs引发免疫反应和针对口蹄疫病毒(FMDV,最具毁灭性的家畜疾病之一)产生保护作用的能力。为此,我们构建了一组包含两个源自FMDV的表位的嵌合VLPs:一个中和性B细胞表位(VP1(140 - 158))和一个T细胞表位[3A(21 - 35)]。这些表位被插入到RHDV衣壳蛋白内的两个不同位置,或是连接在一起插入,或是单独插入。在小鼠和猪模型中分析了嵌合VLPs的免疫原性和保护潜力。在此我们表明,展示源自FMDV表位的工程化RHDV VLPs在小鼠和猪中引发了强大的中和免疫反应,为猪提供了针对FMDV攻击的部分临床保护。