Exploring viral mutational trajectories with protein engineering

Researcher: Dr William Kelton

Marsden

Zoonotic viruses like coronavirus can mutate and move from animals to humans. In collaboration with researchers at ETH Zurich, we are using advances in protein engineering and machine learning to predict how viruses accumulate mutations that might contribute to new variants before they have the opportunity to do so. These steps are being undertaken without the use of live virus, instead, fragments from the viral surface are presented on the surface of yeast cells where they are accessible for binding protein entry receptors.

The advance prediction of viral mutational avenues could be useful in enabling an early warning system for new and emerging viruses, especially those jumping from animals. We will create a series of models that predict entry receptor binding from sequence alone.

Smart antigens for hyperimmune milk products

Researcher: Dr William Kelton

MBIE Smart Idea

Recent viral outbreaks have highlighted the need for products that can provide immediate, short-term protection against infection as a complement to vaccination or when vaccines are not yet available. One potential solution is to use antibodies, immune molecules that bind to and block the function of viruses. Producing sufficient antibodies for population-scale deployment can be difficult but significant quantities are naturally produced in the milk of ruminant species like sheep and cows. The challenge is to efficiently direct these antibody responses against viruses of concern.

Working alongside Ruakura Technologies Ltd, we will improve antiviral antibody induction in ruminants using a new class of molecular Smart-Antigens. These designer protein molecules fuse elements of the sheep’s own immune system with viral components to massively increase the production of antibodies after immunisation. We will target the viral pathogen norovirus for which no vaccine currently exists, and treatment options are few.