Plant-based production of a vaccine against gonorrhoea

The principal BBSRC priority area addressed by this project is 'Bioscience for renewable resources and clean growth - transforming industries through bio-based processes and products in a new low-carbon bioeconomy'. The project has a focus on plant biotechnology and therefore fits firmly within the BBSRC ambit. The proposal will introduce ways to improve the performance of vaccine production; in particular, transition to plant-based expression offers the potential for much reduced production energy costs, particularly in low income countries. Further, the targeting of antigen presenting cells is a disruptive technology, in the sense that it has the potential to overtake non-target vaccine approaches and thus address disease where induction of protective immunity is a major roadblock to vaccine development.

The emergence of antimicrobial resistance (AMR) in Neisseria gonorrhoeae (Ng) has made combatting this bacterium an international priority. Ng is a leading cause of sexually transmitted infection (STI), responsible for >100 million cases annually. The inability to treat Ng adversely impacts female reproductive and foeto-maternal health (through pelvic inflammatory disease, ectopic pregnancy, infertility), while gonococcal infection is an important co-factor for HIV transmission. Furthermore, control of the gonococcal (Gc) transmission is threatened by the rise in antibiotic resistance. While vaccines are an important approach against the threat of resistant bacteria, Gc vaccine research has been hampered by the lack of protective immunity following infection, antigenic variation and previous failed attempts. However, recent advances have provided fresh impetus for vaccine development- an outer membrane vesicle vaccine (OMV) used against Neisseria meningitidis was associated with a modest yet significant protection against Ng, suggesting an approach to identify protective antigens. Vaccination strategies based on single recombinant Ng antigens have met with limited success, both in mouse infection models and clinical trials. A novel approach would be to use virus-like particles (VLPs)- or the more recently introduced large, synthetic macromolecular assemblies- as platforms for antigen delivery. These developments offer a hitherto untapped potential in vaccine design. In addition, the Derrick lab has recently developed a technology which allows the fusion of any number of antigens to a specific VLP or assembly. Critically, the method also allows for facile fusion of monoclonal antibodies: incorporation of antibodies directed against surface receptors thus allows targeting against specific subsets of dendritic or other antigen presenting cells. This development promises a game-changing approach to vaccine design, by combining target-driven antibody therapeutic technologies with traditional vaccine design. It could provide the breakthrough needed to circumvent the challenge of weak protective immunity against Ng reinfection. In addition, there is increasing interest in the use of plant-based expression systems for biopharmaceuticals and vaccines, particularly for application in developing countries. This project therefore aims to exploit methods developed by Anil Day for plastid-based expression, which enables very high yields of recombinant proteins, and apply them to modified VLPs, assemblies and Ng antigens.