Prime-boost vectored malaria vaccines Progress and prospects
Prime-boost vectored malaria vaccines Progress and prospects
复制标题
DOI：
10.4161/hv.6.1.10116
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Draper, Simon J.
中科院分区：
文献类型：
--
作者：
Hill, Adrian V. S.;Reyes-Sandoval, Arturo;Draper, Simon J.
通过针对子孢子的抗体诱导保护性免疫的困难导致了评估载体疫苗作为诱导针对疟疾肝脏阶段寄生虫的保护性T细胞免疫的手段的努力。尽管单独使用的DNA载体疫苗免疫原性差且不具有保护性，但在异源初免-加强方案中使用的病毒载体疫苗已经实现了肝脏中高水平的寄生虫清除。这种载体疫苗接种方案代表了在人恶性疟原虫亚单位疫苗试验中诱导可重复的部分功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有效的T细胞应答，这目前只能用异源初免-加强方案实现。最近，在英国的I期和IIa期试验中，猴腺病毒已被评估为腺病毒-MVA方案中的引发剂，这是基于非常有希望的临床前结果，其显示出比先前的引发-加强方案更好的免疫原性和功效。同样的载体也在临床上进行评估，表达血液阶段抗原，试图诱导保护性抗体和T细胞，如最近在小鼠功效研究中所证明的。这些病毒载体现在提供了一个主要的选择，包括在一个高效率的多阶段疟疾疫苗，应达到部署水平的效力在地方性环境。
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.