(89e) Engineering a New Rapid-Response Vaccine Capability

In chemical engineering, the concept of a timely response to disturbance is taught in undergraduate courses. A complex system subject to disturbance is controlled by actions that mitigate the impact of disturbance before that disturbance magnifies to disrupt the entire system. The time constant of response must be smaller than the time constant over which the disturbance will amplify. In vaccine engineering, this is not presently the case. The disturbance (e.g. a virus) can propagate faster than we can mount a vaccine response. This fact was amply demonstrated by the (H1N1) 2009 pandemic which led to social disruption and strain on the health system, even though the disease was mild in most cases. Also central in chemical engineering is the concept of a product made to a cost the market can afford. Although vaccination has led to the eradication of smallpox, around 15 million people still die annually from infectious disease, with more than half of them being children under the age of 5. A new vaccine engineering paradigm is urgently needed. Here we report a new manufacturing approach which starts with non-infectious protein and builds structure, and hence antigenicity, without building infectivity. Our approach relies on the expression and purification of proteins prepared in bacterial cell factories which are then processed in vitro into virus-like particles (VLPs). Protein production in highly efficient bacteria maximises speed and efficiency while also minimising the need for high-level biocontainment during manufacture. The approach is both exciting and challenging, raising a number of research questions amenable to solution by chemical engineers. Combined, these aspects have the potential to move us toward a vaccine future based on fundamental chemical and molecular engineering, using fast, scaleable and cheap technological approaches.