Lundstrom Kenneth
PanTherapeutics, Rue des Remparts 4, Lutry, 1095, Switzerland.
Methods Mol Biol. 2017;1581:225-242. doi: 10.1007/978-1-4939-6869-5_13.
Alphavirus-based vectors have been engineered from Semliki Forest virus, Sindbis virus, and Venezuelan equine encephalitis virus and applied for vaccine development. Immunization in preclinical animal models has been conducted with naked RNA replicons, recombinant viral particles and layered DNA-RNA vectors. Most commonly, the targets for the immunization have been viral surface proteins and tumor antigens, which have elicited strong immune responses and even provided protection against challenges with lethal doses of virus and tumor cells, respectively. As alphaviruses also cause epidemics, vaccines have been developed against Chikungunya virus. Despite the success in several animal smodels only a few clinical trials have been conducted in humans, so far.
基于甲病毒的载体已从辛德毕斯病毒、塞姆利基森林病毒和委内瑞拉马脑炎病毒改造而来,并应用于疫苗研发。已在临床前动物模型中使用裸露的RNA复制子、重组病毒颗粒和分层DNA-RNA载体进行免疫接种。最常见的免疫接种靶点是病毒表面蛋白和肿瘤抗原,它们分别引发了强烈的免疫反应,甚至提供了针对致死剂量病毒和肿瘤细胞攻击的保护作用。由于甲病毒也会引发疫情,因此已经研发出了针对基孔肯雅病毒的疫苗。尽管在多个动物模型中取得了成功,但迄今为止,仅在人类中进行了少数临床试验。