Engineering plants to produce vaccines

Plants are increasingly being investigated as alternative production systems for recombinant proteins. Technological advances allow either transient expression methods or the establishment of permanent plant lines that produce stable target proteins.

The EU-funded PLAPROVA (Plant production of vaccines) project has exploited plant expression systems to screen a range of vaccine candidates. Project partners focused on the development of virus-like particles (VLPs) against important diseases of livestock such as avian influenza virus and bluetongue. VLPs stimulate the immune system and can therefore be used as vaccines.

Researchers used plant viruses such as the cowpea mosaic virus (CPMV) and the tobacco mosaic virus (TMV) for delivery and transient expression of vaccine antigens in plants. Refinement of the CPMV system enabled the simultaneous expression of multiple polypeptides within one plant cell.

Scientists expressed VLPs consisting of a single polypeptide and also more complex, multi-chain VLPs in plants. .At least four proteins could be co-expressed in a controlled manner using bluetongue virus (BTV) capsids in tests. These successfully assembled into complex VLPs demonstrating their functional capacity.

Purified, assembled VLPs were administered to experimental animals to determine their antigenic and immunogenic properties. Complex VLPs from BTV protected sheep against viral challenge. Similarly, a plant-expressed foot and mouth disease virus polyepitope was successfully used to vaccinate guinea pigs.

An important achievement of the project was the expression of candidate prophylactic vaccines against human papillomavirus and bovine papilloma virus. Using a novel membrane protein (M2e) as an immunogen, TMV particles protected mice against Asian influenza virus.

Scientists also managed to tackle the prior toxicity of porcine respiratory and reproductive syndrome virus proteins expressed in plants. To achieve this, they engineered proteins with reduced toxicity and genetic instability while retaining their immunological properties.

The PLAPROVA initiative has demonstrated that it is possible to produce high levels of proteins in plants for subsequent use as vaccines. Low production costs will endow important economic benefits to both the pharmaceutical and agricultural industries.