Vectored Blood Stage Malaria Vaccine

疟疾是全球感染性死亡的最大原因之一，但没有疫苗可用。寄生虫的血液阶段？的生命周期是一个导致所有症状的疾病，往往死亡。许多针对这一阶段的疫苗已经在临床试验中进行了测试，但结果总是令人失望。然而，所有这些疫苗都含有寄生虫的蛋白质成分，并混合了一种化学佐剂，旨在尝试增加对疫苗的免疫反应。各种不同类型的疫苗现在在其他疾病，如艾滋病毒/艾滋病、肺结核，甚至疟疾的肝脏阶段显示出希望。这些载体疫苗使用一种残缺的安全病毒在接种者的注射部位内产生疟疾抗原。这产生对蛋白质/佐剂疫苗的定性和定量不同的免疫应答。使用啮齿动物疟疾模型，我们发现使用这种载体疫苗对血液阶段疟疾具有很好的保护作用，并继续制造针对主要人类寄生虫恶性疟原虫的相应载体。在本申请中，我们建议首次在人类中测试一对针对疟疾血液阶段的载体疫苗。我们将使用一个完善和安全的传染性蚊子叮咬程序来测试疫苗是否对志愿者有效。这项研究应该提供一个关键的测试的可能性，这种载体疫苗可能是有用的，在保护人们免受疟疾的重要血液阶段。

Malaria is one of the greatest causes of infectious mortality globally but no vaccine is available. The blood-stage of the parasite?s life-cycle is the one that causes all the symptoms of disease and very often death. Many vaccines against this stage have been tested in clinical trials but always with disappointing results. However, all these vaccine comprised protein components of the parasite mixed with a chemical adjuvant designed to try and increase the immune response to the vaccine. Quite different types of vaccine are now showing promise in other diseases such as HIV/AIDS, tuberculosis and even the liver-stage of malaria. These vectored vaccines use a crippled safe virus to produce the malaria antigen inside the injection site of the vaccinee. This generates qualitatively and quantitatively different immune responses to protein/adjuvant vaccines. Using a rodent malaria model we have found excellent protection using such vectored vaccines against blood-stage malaria and have gone on to make the corresponding vectors that target the major human parasite Plasmodium falciparum. In this application we propose to test a pair of vectored vaccines against the blood-stage of malaria for the first time in humans. We will use a well developed and safe infectious mosquito biting procedure to test whether the vaccine is effective in volunteers. This study should provide a critical test of the possibility that such vectored vaccines could be useful in protecting people against the important blood-stage of malaria.