Vaughan Ashley M, Wang Ruobing, Kappe Stefan H I
Seattle Biomedical Research Institute, Seattle, WA, USA.
Hum Vaccin. 2010 Jan;6(1):107-13. doi: 10.4161/hv.6.1.9654. Epub 2010 Jan 29.
Malaria remains one of the most significant infectious diseases affecting human populations in developing countries. The quest for an efficacious malaria vaccine has been ongoing for nearly a century with limited success. The identification of malaria parasite antigens focused efforts on the development of subunit vaccines but has so far yielded only one partially efficacious vaccine candidate, RTS/S. The lack of high vaccine efficacy observed to date with subunit vaccine candidates raises doubts that the development of a single antigen or even a multi-antigen malaria subunit vaccine is possible. Fortunately, it has been demonstrated in animal studies and experimental clinical studies that immunizations with live-attenuated sporozoite stages of the malaria parasite confer long lasting, sterile protection against infection, providing a benchmark for vaccine development. These early successful vaccinations with live-attenuated malaria parasites did not however, promote a developmental path forward for such a vaccine approach. The discovery of genetically engineered parasite strains that are fully attenuated during the early asymptomatic liver infection and confer complete sterile protection in animal malaria models support the development of a live attenuated sporozoite vaccine for Plasmodium falciparum and its accelerated safety and efficacy testing in malaria challenge models and in malaria endemic areas.
疟疾仍然是影响发展中国家人口的最重要传染病之一。寻求有效的疟疾疫苗已经进行了近一个世纪，但成效有限。对疟原虫抗原的鉴定促使人们致力于亚单位疫苗的研发，但迄今为止仅产生了一种部分有效的疫苗候选物RTS/S。目前观察到亚单位疫苗候选物缺乏高疫苗效力，这让人怀疑是否有可能开发单一抗原甚至多抗原疟疾亚单位疫苗。幸运的是，动物研究和实验临床研究已经证明，用减毒活疟原虫子孢子阶段进行免疫可提供针对感染的持久、无菌保护，为疫苗开发提供了一个基准。然而，这些早期用减毒活疟原虫进行的成功疫苗接种并没有推动这种疫苗方法的进一步发展。在动物疟疾模型中发现的基因工程寄生虫菌株，在早期无症状肝脏感染期间完全减毒并提供完全的无菌保护，这支持了恶性疟原虫减毒活子孢子疫苗的开发及其在疟疾攻击模型和疟疾流行地区的加速安全性和有效性测试。
