A novel production system for virus-like particle vaccines

One of the greatest challenges to human and animal health, particularly to young adults, is the
threat of emerging infectious diseases, which can spread rapidly across countries and through
unprotected populations. Many of these threats come from virus diseases, in which mutations
enables a virus to spread into new animal or human populations. It is therefore important that
we can respond by the production of new vaccines in a timely manner. Effective vaccines to
many virus diseases can be made by immunising people or animals with a non-infectious
particle that mimics the infectious agent; such particles are usually referred to as virus-like
particles (VLPs). In recent years it has been shown that an insect-specific virus, a baculovirus
(BV), can be used as a tool to deliver the blueprint for the target vaccine VLP into an insect
host cell, which then acts as a factory to produce large quantities of the required VLP vaccine.
This so called 'BV system' is safe, because only insect viruses are used; is rapid, new VLP
vaccines can be produced in a just a few weeks; and is easily scalable to produce 1000's
vaccine doses. BV-derived vaccines have already been approved for use in animals and
humans and so have a successful track record. However, as more VLPs have been produced
in insect cells, a significant hurdle has been discovered; in many cases it is difficult to
separate the desired VLP from the baculovirus particle and this has lead to time consuming
and laborious purification techniques that have often led to poor yields or even no useful VLP
product at all. Our project aims to address this technical challenge by testing a novel BV
system in which we can control production of the baculovirus particle, by using what is
essentially a molecular on/off switch. If our control system works, we will be able to switch
off BV particle synthesis at the time of target VLP production and thus avoid the need for any
further purification steps.