Guillain Barre syndrome antibodies during Zika and Cikungunya vaccine trials

寨卡和奇孔肯雅疫苗试验中的格林巴利综合征抗体

• 批准号: 971540
• 金额: $ 34.63万
• 依托单位: IMPERIAL COLLEGE LONDON
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=971540
• 关键词: Guillain; Barre; syndrome; antibodies; during

There is considerable concern over human viral infections caused by Zika virus and Chikungunya virus. In 2016 the WHO declared Zika a 'Public Health Emergency of International Concern,' flagging up specifically the lack of vaccines and of reliable diagnostic tests. Both infections are spread by Aedes egyptii mosquitoes. Zika infection is thought to be asymptomatic in a majority of exposed individuals, to cause symptoms such as rash and conjunctivitis in about 20% and is more rarely associated with neurological symptoms, including microcephaly in the newborn and Guillain-Barré syndrome (GBS) in adults. GBS can follow a number of infections (or, occasionally, vaccinations) including also Chikungunya. GBS is an acute paralysis seen as weakness that can affect breathing as well as the arms, legs and face. The mechanism is poorly understood but is believed to involve cross-reactive antibody targeting of glycolipid structures common to the the microbial pathogens and the human nervous system. It has been hard to develop widely applicable diagnostic tests and GBS is commonly diagnosed on the clinical assessment of a neurologist. The broad case for improved diagnostic platforms for GBS is readily made, but the need is all the more pressing in light of the current and forthcoming roll-out of new vaccine trials in regions most impacted by Zika and Chikungunya. A large number of Zika candidate vaccines are entering trials, these based on diverse approaches including viral recombinant subunit vaccines, live attenuated vaccines, whole inactivated vaccines and DNA vaccines. It is unknown whether any of these vaccines could cause GBS in some recipients as in 1976 when there was an increased risk of GBS after swine flu vaccination. A key concern voiced by vaccine producers is that any enhancement of such adverse events in Zika or Chikungunya vaccine trials would have devastating impact, including that on conduct of subsequent trials and implementation of related vaccines. However, we lack the tests for high-throughput diagnostic analysis and currently lack even basic disease surveillance on the seroprevalence of these GBS antibodies in the test populations. Here we bring together synergistic teams to harness neuroimmunologists with strong ZIka collaborations in Brazil, a glycobiology research team with unique resources for high-throughput analysis of glycoarray libraries with the wherewithal to translate GBS biosignature discovery into a simple, affordable kit. We see our technology as offering a safety-net to underpin development of Flavivirus vaccination programmes. We will start with a Discovery Phase, using GBS cohort sera to progress from comprehensive gylcolipid array libarary screening to a diagnostic probe set of high senstivity and specificity, which can be developed during the Development/Implementation Phase into a simplified, commercially affordable GBS diagnostic. The work is of high relevance to LMIC countries and will be conducted in collaboration with researchers in highly affected regions of Brazil.

寨卡病毒和基孔肯雅病毒引起的人类病毒感染引起了相当大的关注。2016年，世界卫生组织宣布寨卡病毒为“国际关注的突发公共卫生事件”，并特别指出了缺乏疫苗和可靠的诊断测试的问题。这两种感染都是由埃及伊蚊传播的。寨卡病毒感染被认为在大多数接触者中没有症状，大约20%的人会导致皮疹和结膜炎等症状，较少与神经系统症状有关，包括新生儿的小头畸形症和成年人的格林-巴利综合征(GBS)。GBS可以跟随一些感染(或偶尔接种疫苗)，也包括基孔肯雅热。GBS是一种急性瘫痪，被视为虚弱，不仅会影响呼吸，还会影响手臂、腿和面部。其机制尚不清楚，但据信涉及交叉反应抗体靶向糖脂结构的微生物病原体和人类神经系统共同的。很难开发出广泛适用的诊断测试，而GBS通常是通过神经科医生的临床评估来诊断的。改进GBS诊断平台的广泛理由很容易提出，但鉴于目前和即将在受寨卡和基孔肯雅影响最严重的地区推出新的疫苗试验，这一需求更加迫切。大量寨卡候选疫苗正在进入试验阶段，这些疫苗基于不同的方法，包括病毒重组亚单位疫苗、减毒活疫苗、全灭活疫苗和DNA疫苗。目前尚不清楚这些疫苗中的任何一种是否会像1976年那样在一些接受者中引起GBS，当时在接种猪流感疫苗后，GBS的风险增加。疫苗生产商表达的一个关键关切是，寨卡或基孔肯雅疫苗试验中此类不良事件的任何加强都将产生毁灭性的影响，包括对后续试验的进行和相关疫苗的实施。然而，我们缺乏高通量诊断分析的测试，目前甚至缺乏对测试人群中这些GBS抗体血清阳性率的基本疾病监测。在这里，我们聚集了协同团队，利用巴西与寨卡病毒的强大合作来利用神经免疫学家，这是一个糖生物学研究团队，拥有高通量分析糖阵列文库的独特资源，并有必要的资金将GBS生物签名发现转化为简单、负担得起的试剂盒。我们认为我们的技术提供了一个安全网，以支持黄病毒疫苗接种计划的发展。我们将从发现阶段开始，使用GBS队列血清从全面的糖脂阵列文库筛选进展到高灵敏度和特异性的诊断探针组，它可以在开发/实施阶段开发成简化的、商业上负担得起的GBS诊断。这项工作与LMIC国家高度相关，将与巴西受影响严重地区的研究人员合作进行。