Multivalent Antigen Expression and Vaccine for Malaria

描述：(申请人提供)疟疾仍是 影响世界上大量人口的毁灭性疾病，并声称 据估计，每年有一两百万人丧生。不幸的是，目前还没有疫苗 可用于治疗疟疾。目前的候选重组疫苗只有 一种或几种抗原，可阻断疟疾生命周期中的一个阶段，并且 事实证明，这并不有效。我们提出了使用酵母的组合方法。 和杆状病毒利用泛素融合表达至少30个抗原 针对疟疾生命周期的所有三个步骤的技术。多重 现在可以使用新的克隆技术快速表达抗原。 Lifesensors建议将泛素连接到候选者的C末端 疟疾抗原，以显著提高蛋白质的质量和数量。 除了蛋白质表达和折叠的改善外，泛素融合 这项技术允许产生具有不同氨基末端和选择的蛋白质 以产生未裂解的Ub抗原。后者已被证明可以提高CTL 免疫后的反应。该抗原池将在小鼠身上进行测试 恶性疟原虫的免疫应答及免疫荧光研究 定位抗原相互作用。该SBIR的第二阶段将包括 抗原数量的增加，临床级材料的生产 作为猴子模型的测试。我们相信，一种高效的方法 表达多种泛素化抗原将是一种新的解决方案 疟疾疫苗的开发。

DESCRIPTION: (Provided by Applicant) Malaria continues to be one of the devastating diseases affecting a large population of the world and claims an estimated one to two million lives annually. Unfortunately, there is no vaccine available against malaria. Current recombinant vaccine candidates are only of one or of few antigens that block one stage in the malaria life cycle and are proven not to be effective. We propose combinatorial approach by using yeast and baculovirus to express at least 30 antigens using ubiquitin-fusion technology that targets all three steps in malaria life cycle. Multiple antigens can now be expressed rapidly using new cloning technologies. LifeSensors proposes the attachment of ubiquitin to C-terminus of candidate malaria antigens to dramatically enhance quality and quantity of the proteins. Besides the improvement of protein expression and folding, ubiquitin fusion technique allows to generate proteins with different amino termini and a choice to create uncleaved Ub-antigens. The latter has been shown to increase CTL response upon immunization. The pool of antigens will be tested in mice for immune response, as well as immunofluorescence studies with P. falciprum to localize the antigen interaction. Phase II of this SBIR will include an increase in number of antigens, production of clinical grade material, as well as tests in monkey model. We believe that a highly efficient method of expression of multiple and ubiquitinated antigens will be a novel solution in the development of malaria vaccine.