BCR & TCR

Repertoire Analysis

Antibodies are one of our key defences against infectious disease. Our immune systems can make billions of antibody variants to counter the extremely diverse components of infectious organisms that we encounter. With the advent of next-generation sequencing, it is now possible to fully characterise the composition of antibody and T-cell receptor (TCR) sequence repertoires. Particular clones of sequences are expanded during infections according to the antigens encountered, so these sequencing techniques provide a snapshot of how an individual responds to an infectious disease or provide a 'fingerprint' indicating how they responded to past infections.

By combining repertoire sequencing with other molecular methods, we study what makes people immune to infectious diseases. Sometimes the immune system can cause disease itself - we are also analysing the antibodies generated in autoimmune conditions to understand why the immune system can go wrong and how we can prevent it.

Malaria

Vaccine Research

Despite many decades of intense research and development effort, there remains no commercially available malaria vaccine and the most advanced candidate has shown only modest and short-lived protection. Until recently, approaches to antigen discovery relied on empirical testing of recombinant parasite antigens, selected as correlates of protection in seroepidemiological studies. This involves pre-conceptions of which proteins to produce and test, and misleading results can result from such ELISA methods as protected and unprotected individuals can respond to different epitopes of the same protein.

To develop the next generation of malaria vaccines, we need to better understand the mechanisms and antigens that confer clinical protection. We use state of the art molecular techniques to detect how the immune system adapts to malaria to inform better vaccine design. The use of these techniques to provide better information on how patients react in clinical trials for malaria vaccines could also help understand better how candidate vaccines have performed and how to improve them.