Developmental Clinical Studies - Clinical evaluation of an AdCh63-MVA PvDBP_RII vaccine for blood-stage Plasmodium vivax

发育性临床研究 - AdCh63-MVA PvDBP_RII 血液期疟原虫疫苗的临床评估

• 批准号: G1100086/1
• 负责人: Simon Draper
• 金额: $ 114.1万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1100086%2F1
• 关键词: Developmental; Clinical; Studies; evaluation; AdCh63

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. Five different types of parasite cause malaria disease in humans. Most research in the last few decades has focussed on one of these parasites ? called Plasmodium falciparum. This parasite is responsible for most of the deaths every year due to malaria infection.Many vaccines against blood-stage infection with Plasmodium falciparum have been tested in clinical trials but always with disappointing results. This is most likely because this parasite has many different ways to infect red blood cells. Consequently if a vaccine stops one invasion pathway, the parasite will simply switch to a different one and continue with the infection process.A second malaria parasite, called Plasmodium vivax, is far more widespread worldwide. Although it doesn?t kill infected individuals, infection with this parasite causes a debilitating and severe illness that often relapses months or years later. This parasite, like Plasmodium falciparum, exerts a huge and unacceptable health burden on the wider developing world. However, this parasite may be more amenable to the effects of a blood-stage vaccine. It can only use a single invasion pathway to infect red blood cells, and a vaccine targeting this one pathway may stand a much greater chance of success. Here we propose to use a new vaccine delivery technology to target this invasion pathway of Plasmodium vivax. Vectored vaccines use a crippled but safe virus to produce the malaria protein inside the injection site of the vaccinee. This technology has recently been shown to be safe and capable of inducing strong immune responses in human clinical trials at Oxford University. In this application we therefore propose to test a new pair of vectored vaccines against the blood-stage of Plasmodium vivax malaria for the first time in humans. We will develop these new vaccines and test their safety and immune-stimulating capacity in a clinical trial in healthy adult volunteers. This study should provide a critical test of the possibility that such vectored vaccines could be useful in inducing immune responses that may protect people against infection with the Plasmodium vivax form of malaria.

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。五种不同类型的寄生虫导致人类疟疾疾病。在过去的几十年里，大多数研究都集中在这些寄生虫中的一种上。叫做恶性疟原虫这种寄生虫是每年因疟疾感染而导致的大多数死亡的原因。许多针对恶性疟原虫血液阶段感染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。这很可能是因为这种寄生虫有许多不同的方式感染红细胞。因此，如果一种疫苗阻止了一种入侵途径，寄生虫就会转向另一种途径，继续感染过程。第二种疟疾寄生虫，称为间日疟原虫，在世界范围内传播得更广。虽然它没有？这种寄生虫的感染不会杀死被感染的个体，但会导致一种使人衰弱的严重疾病，通常在数月或数年后复发。这种寄生虫与恶性疟原虫一样，对广大发展中国家造成巨大和不可接受的健康负担。然而，这种寄生虫可能更容易受到血液阶段疫苗的影响。它只能使用单一的入侵途径来感染红细胞，针对这一途径的疫苗可能会有更大的成功机会。在这里，我们建议使用一种新的疫苗输送技术，针对这一入侵途径的间日疟原虫。载体疫苗使用一种残废但安全的病毒在接种者的注射部位内产生疟疾蛋白。这项技术最近在牛津大学的人体临床试验中被证明是安全的，并且能够诱导强烈的免疫反应。因此，在本申请中，我们建议首次在人类中测试一对新的针对间日疟原虫疟疾血液阶段的载体疫苗。我们将开发这些新疫苗，并在健康成年志愿者的临床试验中测试其安全性和免疫刺激能力。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诱导免疫反应，可能会保护人们免受疟疾的间日疟原虫形式的感染。