Hill Adrian V S, Reyes-Sandoval Arturo, O'Hara Geraldine, Ewer Katie, Lawrie Alison, Goodman Anna, Nicosia Alfredo, Folgori Antonella, Colloca Stefano, Cortese Riccardo, Gilbert Sarah C, Draper Simon J
The Jenner Institute, University of Oxford, Oxford, UK.
Hum Vaccin. 2010 Jan;6(1):78-83. doi: 10.4161/hv.6.1.10116. Epub 2010 Jan 18.
The difficulty of inducing protective immunity through antibodies against sporozoites led to efforts to assess vectored vaccines as a means of inducing protective T-cell immunity against the malaria liver-stage parasite. Although DNA vectored vaccines used alone were poorly immunogenic and not protective, high levels of parasite clearance in the liver has been achieved with viral vectored vaccines used in heterologous prime-boost regimes. Such vectored vaccination regimes represent one of only two approaches that have induced repeatable partial efficacy in human P. falciparum subunit vaccine trials. Interestingly, vectors expressing the TRAP antigen have been consistently been more immunogenic and protective than vectors expressing the circumsporozoite protein in human trials. However, sterile protection requires induction of very potent T-cell responses that are currently only achievable with heterologous prime-boost regimes. Recently, simian adenoviruses have been assessed as priming agents in Adenovirus-MVA regimes in both phase I and phase IIa trials in the UK, based on very promising pre-clinical results showing better immunogenicity and efficacy than previous prime-boost regimes. The same vectors are also being assessed clinically expressing blood-stage antigens, attempting to induce both protective antibodies and T cells as recently demonstrated in murine efficacy studies. These viral vectors now provide a major option for inclusion in a high efficacy multi-stage malaria vaccine that should achieve deployable levels of efficacy in endemic settings.
通过针对子孢子的抗体诱导保护性免疫存在困难，这促使人们努力评估载体疫苗，将其作为诱导针对疟疾肝期寄生虫的保护性T细胞免疫的一种手段。尽管单独使用的DNA载体疫苗免疫原性较差且无保护作用，但在异源初免-加强免疫方案中使用的病毒载体疫苗已在肝脏中实现了高水平的寄生虫清除。这种载体疫苗接种方案是在人类恶性疟原虫亚单位疫苗试验中诱导出可重复的部分疗效的仅有的两种方法之一。有趣的是，在人体试验中，表达TRAP抗原的载体一直比表达环子孢子蛋白的载体更具免疫原性和保护性。然而，无菌保护需要诱导非常强效的T细胞反应，而目前只有通过异源初免-加强免疫方案才能实现。最近，基于非常有前景的临床前结果，即显示出比以前的初免-加强免疫方案更好的免疫原性和疗效，猿猴腺病毒已在英国的I期和IIa期试验中被评估为腺病毒-MVA方案中的初免剂。相同的载体也正在进行表达血期抗原的临床评估，试图诱导保护性抗体和T细胞，正如最近在小鼠疗效研究中所证明的那样。这些病毒载体现在为纳入高效多阶段疟疾疫苗提供了一个主要选择，这种疫苗应在流行地区达到可部署的疗效水平。
