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

甲型流感病毒引起一种高度传染性的急性发热呼吸道疾病，每年造成25万至50万人死亡。流感的破坏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细胞反应迅速减弱，要求每年接种疫苗；可靠地预测多价疫苗应该针对哪些毒株是极具挑战性的；而且疫苗繁殖必须在每个呼吸季节前几个月开始。如果发生大流行，在确定大流行毒株和大规模推广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，因为由于流感在两个呼吸季节的传播中断，人口对流感的预先免疫水平低于通常水平。由于这些原因，治疗方法作为对流感的额外缓解措施至关重要。治疗方法是对流感重要的额外缓解措施。然而，当前针对流感的抗病毒药物有很大的局限性，包括必须尽早给药才能有效，并可能选择耐药性。因此，迫切需要额外的治疗选择。人IgG的Fc（片段结晶）已被安全地用于治疗特发性血小板减少症的儿童。因此，我们将对Fc进行修饰，使其富含一种叫做唾液酸的糖，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。从抗体中提取的Fc具有许多优势，使其具有商业吸引力；包括在现有的IgG单克隆抗体（mab）开发管道中易于制造，比大型mab更具优势的商品成本概况，以及在儿童中被证明的安全性和有效性，这些都比其他尚未批准临床使用的方法提供了竞争优势。通过预防、控制和治疗流感，我们的工作通过提供传统单克隆抗体或小化合物分子的改进和更实惠的替代方案，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。

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.