Building novel vaccines on a borrowed coat

描述（由申请人提供）：疫苗接种（或主动免疫）需要将外来物质（抗原）引入个体，以产生对特定疾病的保护（免疫）。简单地说，接种疫苗是通过启动免疫系统来识别特定抗原来起作用的。疫苗接种的主要目标之一是产生抗体的保护效价，以及通过产生能够抵抗感染因子的记忆B细胞来提供长期保护。成功的疫苗必须产生中和抗体反应以及B细胞对特定病原体的记忆。然而，成功的疫苗是例外：很难研制出针对许多传染病（如艾滋病毒）的保护性疫苗，甚至很难研制出针对常见疾病（如流感）的长效保护性疫苗。尽管进行了多年的基础研究，但大多数疫苗失败的原因尚不清楚。近年来，针对非传染性疾病的被动免疫也显示出很大的希望。（这在癌症领域得到了最好的说明，大多数新药的非专利名称以-mab结尾，这是单克隆抗体来源的首字母缩写）。提高治疗性抗体的主动免疫是下一个合乎逻辑的步骤。因此，了解如何制造好的疫苗对传统的传染病和非传染性疾病都有治疗意义，其中大多数疾病目前是无法治愈的。为了解决这两种情况下对成功疫苗的迫切需求，我们建议以一种全新的方式来设计疫苗：而不是试图设计一种免疫原性载体，我们试图利用一种具有内在能力的生物体，这种生物体可以刺激受感染个体产生非常强烈的B细胞反应，从而产生巨大的抗体和B细胞记忆。我们利用非洲布鲁氏锥虫的表皮创造了一种新的疫苗载体，布鲁氏锥虫是一种细胞外寄生虫，生活在受感染的哺乳动物宿主的血液中。布鲁氏杆菌完全暴露在免疫系统中，为了逃避免疫系统，它用它的外衣作为诱饵：它促进对它产生抗体反应，然后换掉外衣，再次开始这个循环，并建立慢性感染。利用布鲁氏杆菌对其外膜产生强烈中和抗体反应（和B细胞记忆）的能力，使其成为最佳（尽管显然是完全非常规的）疫苗载体，我们在此建议将其用于开发针对阿尔茨海默氏症的治疗性疫苗，也用于治疗滥用药物（尼古丁；阿片类药物）。最后，我们希望从布鲁氏杆菌中学习，这样在未来我们就可以开发出设计疫苗，不断模仿这种生物进化的结果。

DESCRIPTION (provided by applicant): Vaccination (or active immunization) entails the introduction of a foreign material (antigen) into an individual in order to produce protection (immunity) to a particular disease. In simple terms, vaccination works by priming the immune system to recognize a particular antigen. One of the primary goals of vaccination is to generate protective titers of antibody, as well as long-term protection through the creation of memory B cells that can protect against the infectious agent. Successful vaccines must generate neutralizing antibody responses as well as B cell memory toward a specific pathogen. However, successful vaccines are the exception: it has been difficult to create a protective vaccine for a great number of infectious diseases (e.g. HIV) or even long lasting, protective vaccines against common diseases (e.g. flu). Despite many years of basic research, the reasons why most vaccines fail are not understood. In recent years, passive immunization against non-communicable diseases has also shown great promise. (This is best illustrated in the context of cancer, where the non-proprietary name for a majority of new drugs ends in -mab; an acronym that indicates the monoclonal antibody source). Active immunization to raise therapeutic antibodies is the next logical step. Therefore, understanding how to make good vaccines is of therapeutic interest both in the traditional context of infectious diseases and in the context of non- communicable diseases, most of which are currently incurable. To address this acute need for successful vaccines in both contexts, we propose to approach vaccine design in a completely new manner: rather than attempt to engineer an immunogenic vector, we sought to exploit an organism that has an inherent ability to stimulate a very strong B cell response in an infected individual, that results in tremendous antibody production and B cell memory. We have created a novel vaccine vector using the coat of the African trypanosome Trypanosoma brucei, an extracellular parasite that lives in the bloodstream of the infected mammalian host. T.brucei is completely exposed to the immune system and to evade it, it uses its coat as a decoy: it promotes the generation of antibody responses to it, and then switches coats, starting the cycle again, and establishing a chronic infection. Exploitation of T.brucei 's ability to elicit strong neutralizing antibody responses (and B cell memory) to its coat makes it an optimal (though clearly completely unconventional) vaccine vector, and we propose herein to use this in the development of therapeutic vaccines toward Alzheimer's and also toward drugs of abuse (nicotine; opiates). Finally, we hope to learn from T.brucei, so that in the future we can develop designer vaccines that successively mimic what this organism has evolved to achieve.