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

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.