Development of a rapid and facile platform for testing viral escape-resistance of therapeutic antibodies & vaccines & determining escape mutations

疫苗可以非常有效地防止人们因病毒而生病，抗病毒药物可以帮助那些生病的人康复。然而，病毒会进化并获得突变，导致一些病毒变体的出现，这些变体可以部分或完全绕过这些预防和治疗。这些所谓的逃逸变异是危险的，因为它们甚至可以导致接种疫苗的人生病，在最坏的情况下，使我们失去对病毒的保护。很难预测病毒中会发生哪些突变，从而导致药物和疫苗的有效性丧失。该项目旨在开发一种新方法，以非常快速和轻松地测试哪些新药和疫苗仍能最有效地对抗未来的病毒变体，并揭示病毒可能获得的导致逃逸的突变。这种新方法不使用病毒。相反，它使用疫苗和药物通常针对病毒的蛋白质，并测试它们是否仍然有效，以对抗该目标蛋白质的所有可能的突变版本。它还揭示了该病毒可能产生的这种蛋白质的不同变体形式。这种新方法可用于疫苗和药物的开发，以便在变体出现之前选择和开发那些对任何新变体最有效的疫苗和药物。此外，如果不可能产生逃逸抵抗，它还揭示了病毒如何能够逃逸，使我们能够开发适当的后续加强疫苗和药物，以阻断这些逃逸途径，并最有效地保护人口。

Vaccines can be extremely effective for preventing people becoming ill from viruses, and anti-viral medicines can help those who do become ill to recover. However, viruses evolve and can acquire mutations leading to the appearance of some viral variants that can partially or fully by-pass these preventions and treatments. These so-called escape variants are dangerous as they can cause even vaccinated people to become ill, and in the worst case leave us without protection against the virus. It is very difficult to predict what mutations can occur in a virus that will lead to loss of effectiveness of medicines and vaccines. This project aims to develop a new method for very quickly and easily testing which new drugs and vaccines would still work best against future viral variants, and for revealing the mutations the virus could acquire that would lead to escape. This new method does not use viruses. Instead, it uses the protein that the vaccines and drugs normally target in the virus, and tests whether they are still effective against a whole range of possible mutant versions of this target protein. It also reveals the different variant forms of this protein that the virus could produce. This new method could be used during the development of vaccines and drugs to enable those that will be most effective against any new variants to be selected and developed, even before the variants appear. In addition, if escape-resistance is not possible, it reveals how the virus would be able to escape, allowing us to develop the appropriate follow-up booster vaccines and drugs that would block these escape routes and be most effective at protecting the population.