Multivalent Antigen Expression and Vaccine for Malaria

描述：（由申请人提供）疟疾仍然是世界上最严重的疟疾之一。 影响世界大量人口的毁灭性疾病， 估计每年有100万到200万人死亡。不幸的是，没有疫苗 可以用来对抗疟疾。目前的重组疫苗候选物仅为 一种或几种抗原，阻断疟疾生命周期的一个阶段， 被证明是无效的。我们提出了组合的方法，通过使用酵母 和杆状病毒来表达至少30种抗原 针对疟疾生命周期所有三个阶段的技术。多 现在可以使用新的克隆技术快速表达抗原。 LifeSensors提出将泛素连接到候选物的C-末端 疟疾抗原，以显着提高蛋白质的质量和数量。 除了蛋白质表达和折叠的改善，泛素融合 该技术允许产生具有不同氨基末端的蛋白质， 以产生未裂解的Ub抗原。后者已被证明可以增加CTL 免疫反应。将在小鼠中测试抗原池， 免疫应答，以及免疫荧光研究与恶性疟原虫， 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，以及 在猴子模型中进行测试。我们认为，一种高效的方法， 多种和泛素化抗原的表达将是一种新的解决方案， 疟疾疫苗的研制。

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.