ADE, Antibody-dependent enhancement

ADE,抗体依赖性增强
  • 文章类型: Journal Article
    自2019年12月以来,严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)已成为一种新兴的人类病毒,世界人口易患2019年冠状病毒病(COVID-19)。SARS-CoV-2比以前的冠状病毒具有更高的传播能力,由核糖核酸(RNA)病毒性质相关的高突变率,导致SARS-CoV-2变体在全球传播时出现。中和抗体被鉴定为针对COVID-19的即时和直接作用治疗剂。单结构域抗体(sdAb),作为具有非复杂结构和内在稳定性的小生物分子,可以获得与常规抗体相当的抗原结合能力,作为一种有吸引力的中和溶液。SARS-CoV-2刺突蛋白附着于肺上皮细胞上的人血管紧张素转换酶2(ACE2)受体以引发病毒感染,作为潜在的治疗靶点。sdAb已经显示出广泛的中和对SARS-CoV-2的各种突变,有效阻止和预防感染,同时有效阻止突变逃逸。此外,sdAb可以发展成为针对COVID-19的多价抗体或吸入性生物治疗剂。
    With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.
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  • 文章类型: Journal Article
    由SARS-CoV-2引发的COVID-19疫情在全球范围内引发了大量疾病,患有称为多系统炎症综合征(MIS-C)的异常COVID后疾病的儿童,截至2020年4月报告。在这里,我们回顾了儿科患者的临床特征和目前正在使用的预后。已将MIS-C与其他临床状况进行了生动的比较。我们已经讨论了炎症反应的可能病因和基本机制,导致器官衰竭。雄激素受体的参与描绘了青春期以下儿童无症状疾病的可能性,有助于抗体依赖性增强的概念。
    The COVID-19 outbreak sparked by SARS-CoV-2, begat significant rates of malady worldwide, where children with an abnormal post-COVID ailment called the Multisystem Inflammatory Syndrome (MIS-C), were reported by April 2020. Here we have reviewed the clinical characteristics of the pediatric patients and the prognosis currently being utilized. A vivid comparison of MIS-C with other clinical conditions has been done. We have addressed the probable etiology and fundamental machinery of the inflammatory reactions, which drive organ failure. The involvement of androgen receptors portrays the likelihood of asymptomatic illness in children below adolescence, contributing to the concept of antibody-dependent enhancement.
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  • 文章类型: Journal Article
    最近正在爆发的2019年冠状病毒病(COVID-19),随着全球感染病例和死亡率的增长,仍然是一个未解决的问题。新型冠状病毒,严重急性呼吸道综合征冠状病毒2(SARS-CoV-2),针对血管紧张素转换酶2(ACE2)受体,主要导致呼吸系统疾病。尽管获得性免疫和抗性免疫是缓解当前大流行趋势的最重要方面之一;然而,关于感染过程的知识仍然存在很大差距,免疫发病机制,recovery,再感染。
    为了回答有关“COVID-19感染病例中再感染的可能性和可能性”或“SARS-CoV-2感染诱导的免疫抵抗再感染的效率和持续时间”的问题,我们严格评估了当前有关SARS-CoV-2免疫和再感染的报告,并特别强调使用动物模型进行的比较研究,这些研究概括了他们关于保护和再感染的发现。此外,讨论了体液免疫在COVID-19恢复过程中的作用以及ACE2在病毒感染性和发病机制中的作用。此外,本文综述了疾病和恢复条件下的先天免疫和细胞免疫以及炎症反应,并介绍了COVID-19进展和恢复在三个不同阶段的免疫学方面的总体概述。最后,我们根据获得性免疫和再感染的可能性将感染病例分为四个不同的组。
    在这篇综述论文中,我们提出了一种新的策略来预测每个确定类别的再感染可能性.这种分类可能有助于更仔细地分配资源以确定:谁需要进行SARS-CoV-2中和抗体的血清学测试,多少百分比的人口对病毒免疫,谁需要接种疫苗。
    The recent ongoing outbreak of coronavirus disease 2019 (COVID-19), still is an unsolved problem with a growing rate of infected cases and mortality worldwide. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is targeting the angiotensin-converting enzyme 2 (ACE2) receptor and mostly causes a respiratory illness. Although acquired and resistance immunity is one of the most important aspects of alleviating the trend of the current pandemic; however, there is still a big gap of knowledge regarding the infection process, immunopathogenesis, recovery, and reinfection.
    To answer the questions regarding \"the potential and probability of reinfection in COVID-19 infected cases\" or \"the efficiency and duration of SARS-CoV-2 infection-induced immunity against reinfection\" we critically evaluated the current reports on SARS-CoV-2 immunity and reinfection with special emphasis on comparative studies using animal models that generalize their finding about protection and reinfection. Also, the contribution of humoral immunity in the process of COVID-19 recovery and the role of ACE2 in virus infectivity and pathogenesis has been discussed. Furthermore, innate and cellular immunity and inflammatory responses in the disease and recovery conditions are reviewed and an overall outline of immunologic aspects of COVID-19 progression and recovery in three different stages are presented. Finally, we categorized the infected cases into four different groups based on the acquired immunity and the potential for reinfection.
    In this review paper, we proposed a new strategy to predict the potential of reinfection in each identified category. This classification may help to distribute resources more meticulously to determine: who needs to be serologically tested for SARS-CoV-2 neutralizing antibodies, what percentage of the population is immune to the virus, and who needs to be vaccinated.
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  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19)已经演变成一场全球人类悲剧和经济破坏。各国政府已经实施了封锁措施,阻止国际旅行,并实施其他公共控制措施,以减轻病毒的发病率和死亡率。截至今天,没有任何药物有能力对抗感染,给彻底的混乱带来常态。这使我们只有一个选择,即一种有效和安全的疫苗,该疫苗应尽快制造,并以负担得起的价格提供给受大流行影响的所有国家和人口。国际社会在研发方面采取了前所未有的快速道路来开发有效和安全的疫苗。平台技术已经被用来在几天到几周内开发候选疫苗,到目前为止,有108种疫苗。其中6种疫苗已进入临床试验。由于临床试验是“限速”和“耗时”,许多创新方法正在实践中,以实现快速通道。这些包括平行I-II期试验和从IIb期试验获得疗效数据。正在认真考虑人类的“挑战实验”以确认其在人类中的功效。COVID-19疫苗的上市已经成为一场在死亡和破坏中与时间的赛跑。COVID-19疫苗周围有一种巨大的炒作气氛,开发人员正在利用每时每刻做出声明,仍未核实。然而,人们担心急于部署COVID-19疫苗。应用“快速修复”和“快捷方式”可能会导致错误,并带来灾难性的后果。
    The coronavirus disease 2019 (COVID-19) has turned into a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks, and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are \"rate-limiting\" and \"time-consuming\", many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human \"challenge experiments\" to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine, and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying \"Quick fix\" and \"short cuts\" can lead to errors with disastrous consequences.
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  • 文章类型: Clinical Trial, Phase II
    Several ChimeriVax-Dengue (CYD)-based vaccination strategies were investigated as potential alternatives to vaccination with tetravalent CYD vaccine (CYD-TDV) in this phase IIa trial conducted in 2008-9 in 150 healthy adults. Participants were randomized and vaccinated on D0 and D105 (± 15 days). One group received bivalent CYD vaccine against serotypes 1 and 3 (CYD-1;3) on day 0 and CYD-2;4 on day 105 (± 15 days). Two groups received an injection at each timepoint of a tetravalent blend of CYD-1;3;4 and a VERO cell derived, live attenuated vaccine against serotype 2 (VDV-2), or the reference CYD-TDV. A fourth group received Japanese encephalitis (JE) vaccine on days -14, -7 and 0, followed by CYD-TDV on day 105. Viraemia was infrequent in all groups. CYD-4 viraemia was most frequent after tetravalent vaccination, while CYD-3 viraemia was most frequent after the first bivalent vaccination. Immunogenicity as assessed by 50% plaque reduction neutralisation test on D28 was comparable after the first injection of either tetravalent vaccine, and increased after the second injection, particularly with the blended CYD-1;3;4/ VDV-2 vaccine. In the bivalent vaccine group, immune response against serotype 3 was highest and the second injection elicited a low immune response against CYD 2 and 4. Immune responses after the first injection of CYD-TDV in the JE-primed group were in general higher than after the first injection in the other groups. All tested regimens were well tolerated without marked differences between groups. Bivalent vaccination showed no advantage in terms of immunogenicity.
    BACKGROUND: NCT00740155.
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  • 文章类型: Journal Article
    Dengue is a major threat for public health in tropical and subtropical countries around the world. In the absence of a licensed vaccine and effective antiviral therapies, control measures have been based on education activities and vector elimination. Current efforts for developing a vaccine are both promising and troubling. At the advent of the introduction of a tetravalent dengue vaccine, molecular surveillance of the circulating genotypes in different geographical regions has gained considerable importance. A growing body of in vitro, preclinical, and clinical phase studies suggest that vaccine conferred protection in a geographical area could depends on the coincidence of the dengue virus genotypes included in the vaccine and those circulating. In this review we present the state-of-the-art in this field, highlighting the need of deeper knowledge on neutralizing immune response for making decisions about future vaccine approval and the potential need for different vaccine composition for regional administration.
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