ICF - Evaluate the potential of AstraZeneca's sialic acid tag technology for treating influenza viruses with Fc molecules

ICF - 评估阿斯利康唾液酸标签技术用 Fc 分子治疗流感病毒的潜力

• 批准号: MR/Y503459/1
• 负责人: Richard Pleass
• 金额: $ 23.85万
• 依托单位: Liverpool School of Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY503459%2F1
• 关键词: ICF; Evaluate; potential; AstraZeneca; sialic

Influenza A virus causes a highly contagious, acute, febrile respiratory illness that kills 250,000-500,000 people every year. The devasting effects of influenza are particularly felt in Africa. Current vaccination strategies face significant limitations, including that antibody and T cell responses wane quickly, mandating annual vaccination programs; it is immensely challenging to reliably predict which strains multivalent vaccines should target; and vaccine propagation must begin several months prior to each respiratory season. In the event of a pandemic, this delay between identification of a pandemic strain and mass rollout of vaccines will inevitably result in huge loss of life and disease burden. Since the lockdowns enforced during the Covid-19 pandemic, the epidemiology of influenza A virus has become even more unpredictable, as population level pre-existing immunity to influenza is lower than typical due to its interrupted circulation over two respiratory seasons. For these reasons, therapeutics are of critical importance as additional mitigations against influenza.Therapeutics are important additional mitigations against influenza. However, contemporary influenza-targeting antivirals, have significant limitations, including that they must be administered early to be efficacious and may select for resistance. Thus, there is an urgent need for additional therapeutic options.The Fc (fragment crystallizable) of human IgG has been administered safely to children in the treatment of idiopathic thrombocytopenia. We will therefore modify the Fc to be rich in a sugar called sialic acid, that interferes with the ability of viruses to bind cell surfaces, thereby preventing virus entry into the cell.Derived from antibodies, the Fc has many advantages that make it commercially appealing; including ease of manufacture in existing pipelines developed for IgG monoclonal antibodies (mAbs), favourable cost-of-goods profiles over larger mAbs, and proven safety and efficacy in children, that provide competitive advantage over other approaches that have yet to be approved for clinical use.By preventing, controlling, and treating influenza, our work addresses one of the overarching goals of the World Health Organisation Global Influenza Strategy 2019-2030, by providing an improved and more affordable alternative to traditional monoclonal antibodies or small compound molecules.

流感病毒会引起高度传染性，急性，高温呼吸道疾病，每年造成250,000-500,000人死亡。非洲尤其感受到流感的破坏性影响。当前的疫苗接种策略面临着重大局限性，包括抗体和T细胞反应迅速减弱，强制性疫苗接种计划；可靠地预测哪些菌株多价疫苗应针对目标是巨大的。疫苗的传播必须在每个呼吸季节前几个月开始。如果发生大流行，鉴定大流行应变与疫苗批量推出之间的延迟将不可避免地导致生命和疾病负担巨大。自从在COVID-19大流行期间强制执行的锁定措施以来，流感病毒的流行病学变得更加不可预测，因为由于人口水平预先存在的流感免疫力低于典型的疾病，因为它在两个呼吸道中的循环中断。由于这些原因，治疗学至关重要，因为对流感的额外缓解作用。治疗学是针对流感的重要缓解。但是，当代靶向抗病毒药物具有重大局限性，包括必须尽早给药才能有效，并且可能会选择抵抗力。因此，迫切需要其他治疗选择。人IgG的FC（片段可结晶）已安全地用于儿童治疗特发性血小板减少症。因此，我们将修改FC富含一种称为唾液酸的糖，从而干扰病毒结合细胞表面的能力，从而防止病毒进入细胞。从抗体中衍生的抗体，FC具有许多优势，使其具有商业吸引力。包括用于IgG单克隆抗体（MABS）的现有管道中的制造易于制造，优惠的良好成本概况比较大的mAbs易于使用，并在儿童中证明了安全性和功效，这些优势比尚未批准临床使用的其他方法提供了竞争优势。通过临床使用，防止和治疗我们的一项策略，即在某种程度上造成的策略，即在某种程度上影响临床的策略，而不是临床的策略，而不是临床的策略，而不是临床的策略，而不是临床的策略。 2019 - 2030年，通过提供传统单克隆抗体或小型化合物分子的改进且更实惠的替代品。