Developing an edible algal vaccine

Rotavirus is an extremely infectious disease, which causes severe diarrhoea in young children and young animals. Although it is controlled by vaccination in humans, it remains a significant issue in farming. It is a leading cause of piglet death, which has serious financial implications: a rotavirus outbreak on an average-sized farm will result in losses of around £20,000. Outbreaks are common.

This project uses synthetic biology to develop an oral, edible vaccine from algae. Algae can be grown in controlled conditions extremely cheaply, and advances in synthetic biology techniques mean that they are now being used for the production of biopharmaceuticals. Several vaccine candidate proteins have been expressed in algae, and this project will be the first to develop an algal rotavirus vaccine.

Rotaviruses are double-stranded RNA viruses. They are classified in genogroups A-J, with rotavirus A (RVA) being the most common in animals and humans. This project will express RVA viral proteins in the green alga Chlamydomonas reinhardtii, a rapidly growing, photosynthetic GRAS (generally regarded as safe) organism. It contains a large chloroplast, and synthetic biology tools have been developed to allow expression of heterologous proteins. The algae have been engineered to remove the ability to carry out photosynthesis. When transformed with the expression vector, photosynthesis is restored. Selection is fast (within one week), and high levels of protein can be expressed. Constructs will be made encoding various different porcine RVA proteins, and these will be used to transform Chlamydomonas. The viral proteins will be purified and used to immunize mice to determine if they cause an immune response. We will also test to see if immunity can be obtained through oral route (i.e. eating the algae), as this would be an ideal method for an animal vaccine.

This innovative technology has been designed by our collaborator Prof. Saul Purton (UCL), and we will be the first to engineer an algal rotavirus vaccine. It is also the first use of an algal vaccine in agriculture, building on the success of the technique in aquaculture (oral vaccination against shrimp white spot disease).

The project will involve training in algal molecular biology, virology and immunology. As the technology is the same for human rotavirus, later work on this project would be to adapt the constructs to produce a rotavirus vaccine against human rotavirus strains.

This joint project will be carried out as a collaboration between microbiologists with expertise in algae (Ellen Nisbet), virology (Ken Mellits) and vaccine specialists (Janet Daly) at the University of Nottingham, in collaboration with Prof. Saul Purton (UCL, algal biotechnology).