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）引入个体体内，以产生针对特定疾病的保护（免疫）。简而言之，疫苗接种的作用是启动免疫系统识别特定抗原。疫苗接种的主要目标之一是产生保护性抗体滴度，以及通过创建可抵御感染因子的记忆 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针对特定病原体的 B 细胞记忆。然而，成功的疫苗是例外：很难研制出针对大量传染病（例如艾滋病毒）的保护性疫苗，甚至很难研制出针对常见疾病（例如流感）的持久保护性疫苗。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了巨大的前景。 （这在癌症的背景下得到了最好的说明，其中大多数新药的非专有名称以 -mab 结尾；这是表示单克隆抗体来源的首字母缩略词）。主动免疫以产生治疗性抗体是下一个合乎逻辑的步骤。因此，了解如何制造良好的疫苗对于传统的传染病和非传染性疾病（其中大多数目前无法治愈）具有治疗意义。 为了满足这两种情况下对成功疫苗的迫切需求，我们建议以全新的方式进行疫苗设计：我们不是试图设计免疫原性载体，而是寻求利用一种生物体，该生物体具有在受感染个体中刺激非常强的 B 细胞反应的固有能力，从而产生大量抗体和 B 细胞记忆。我们利用非洲锥虫布氏锥虫的外壳创建了一种新型疫苗载体，布氏锥虫是一种生活在受感染哺乳动物宿主血液中的细胞外寄生虫。布氏锥虫完全暴露于免疫系统，为了逃避免疫系统，它使用其外壳作为诱饵：它促进对其产生抗体反应，然后转换外壳，再次开始循环，并建立慢性感染。利用布氏锥虫对其外壳引发强烈中和抗体反应（和 B 细胞记忆）的能力，使其成为最佳（尽管显然完全非常规）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和滥用药物（尼古丁；阿片类药物）的治疗性疫苗。最后，我们希望向布氏锥虫学习，以便将来我们可以开发出设计疫苗，以连续模仿这种生物体的进化目标。

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.