Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.

Whole life thinking and engineering the future

Whole-life thinking for engineers working on the built environment has become more important in a fast changing world.Engineers are increasingly concerned with complex systems, in which the parts interact with each other and with the outside world in many ways – the relationships between the parts determine how the system behaves. Systems thinking provides one approach to developing a more robust whole life approach. Systems thinking is a process of understanding how things influence one another within a wider perspective. Complexity, chaos, and risk are endemic in all major projects. New approaches are needed to produce more reliable whole life predictions. Best value, rather than lowest cost can be achieved by using whole-life appraisal as part of the design and delivery strategy.