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.

甲型流感病毒引起高度传染性、急性、发热性呼吸道疾病，每年造成25万至50万人死亡。流感的毁灭性影响在非洲尤其明显。目前的疫苗接种策略面临着重大的局限性，包括抗体和T细胞应答迅速减弱，强制执行年度疫苗接种计划;可靠地预测多价疫苗应该靶向哪些菌株是非常具有挑战性的;并且疫苗繁殖必须在每个呼吸季节之前开始几个月开始。如果发生大流行，从确定大流行毒株到大规模推出疫苗之间的这种延迟将不可避免地导致巨大的生命损失和疾病负担。自2019冠状病毒病大流行期间实施封城以来，甲型流感病毒的流行病学变得更加不可预测，原因是流感在两个呼吸季节中断传播，导致人群对流感的既存免疫力低于一般水平。由于这些原因，治疗药物作为流感的额外缓解措施至关重要。治疗药物是流感的重要额外缓解措施。然而，当代的流感靶向抗病毒药物具有显著的局限性，包括它们必须早期给药才能有效，并且可能选择耐药性。因此，迫切需要额外的治疗选择。Fc（可结晶片段）的人IgG已安全地给予儿童治疗特发性血小板减少症。因此，我们将对Fc进行修饰，使其富含一种称为唾液酸的糖，这种糖干扰病毒结合细胞表面的能力，从而阻止病毒进入细胞。包括在为IgG单克隆抗体（mAb）开发的现有管道中易于制造，优于较大mAb的商品成本概况，通过预防、控制和治疗流感，我们的工作实现了世界卫生组织2019-2030年全球流感战略的总体目标之一，通过提供一种改进的和更可负担的替代传统单克隆抗体或小化合物分子的方法。