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

甲型流感病毒导致一种高度传染性、急性、发烧的呼吸道疾病，每年导致25万至50万人死亡。非洲尤其感受到了流感的毁灭性影响。目前的疫苗接种策略面临着巨大的局限性，包括抗体和T细胞反应迅速减弱，这要求每年进行疫苗接种计划；可靠地预测多价疫苗应该针对哪些菌株是极具挑战性的；以及疫苗传播必须在每个呼吸季节之前几个月开始。一旦发生大流行，从确定大流行毒株到大规模推出疫苗之间的这种拖延将不可避免地导致巨大的生命损失和疾病负担。自新冠肺炎大流行期间实施封锁以来，甲型流感病毒的流行病学变得更加不可预测，因为由于甲型流感病毒在两个呼吸季中断传播，原有的对流感的免疫力低于典型水平。由于这些原因，治疗作为对流感的额外缓解是至关重要的。治疗是针对流感的重要额外缓解。然而，当代针对流感的抗病毒药物有很大的局限性，包括必须及早给予才有效，并可能对耐药性进行选择。因此，迫切需要更多的治疗选择。人免疫球蛋白Fc(片段结晶)已安全地用于儿童特发性血小板减少症的治疗。因此，我们将对Fc进行修饰，使其富含一种名为唾液酸的糖，这种糖会干扰病毒结合细胞表面的能力，从而阻止病毒进入细胞。Fc源于抗体，具有许多优点，使其具有商业吸引力；包括在为免疫球蛋白单抗(MAbb)开发的现有管道中易于制造，相对于较大的mAbs具有良好的商品成本概况，以及在儿童中证明的安全性和有效性，这些都提供了相对于其他尚未被批准用于临床的方法的竞争优势。通过预防、控制和治疗流感，我们的工作解决了世界卫生组织全球流感战略2019-2030年的总体目标之一，提供了一种改进的、更负担得起的替代传统单抗或小化合物分子的方法。

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.