An interview with Professor Judith Breuer

Professor Judith Breuer is Co-director of the Division of Infection and Immunity and Head of the Research Department of Infection at University College London. Her lab focuses on the application of next-generation sequencing and phylogenetic-to-virus diagnostics and discovery. In this interview she tells us how she has used next-generation sequencing to investigate how vaccines work. 

Tell us more about your research

My research encompasses the genomic epidemiology of human disease-causing viruses to inform an understanding of temporal disease patterns, treatment and vaccine strategies. I have focused on viruses of major importance to patients and my clinical practice, including viruses that cause morbidity and mortality in the immunocompromised (herpesviruses, and norovirus). During the course of my research I have pioneered whole genome sequencing of viruses and then hard-to-culture bacteria, directly from clinical material. This has led to an interest in the use of genomics linked to electronic patient records for improving management of antimicrobial resistance. I was awarded £3.3 million in 2019 to establish the infrastructure to support this proposal.

In addition, I have ongoing research projects, which explore whether rapid genome sequencing can be used to interrupt nosocomial spread of viruses; whether genomics can be used to assess the impact of new drugs on serious viral infections, and how genomics and serology can be integrated, to better understand the origins and impact of norovirus pandemics.

Some of your current work focuses on next generation sequencing (NGS), how does this impact understanding how vaccines work?

I use NGS to interrogate the composition of live attenuated vaccines and to investigate vaccine adverse events. This approach has taught me:

• The precise composition of live vaccines: how mixed they are, the allelic frequencies of vaccine mutations, and the stability of the vaccine in different batches.
• Comparing vaccine sequences from adverse events with the original vaccine strain, I have been able to understand more about evolution of human restricted viruses in their natural host – particularly vesicular stomatitis virus (VZV). This has given me insights into pathogenesis, latency, and genetic correlates of vaccine virulence. Applying this approach to the mumps vaccine, encephalitis revealed important likely genetic associations with virulence.
• I have used the genetic data to test function in vitro. In particular, I have discovered the mechanism of attenuation of VZV vaccine, and in doing so have uncovered a new, previously unknown signalling pathway in skin. 

Why does understanding how viruses work matter to microbiology?

Understanding how vaccines work will provide an insight into how they can be improved. This data also provides information on viral pathogenesis and uncovers novel host functions.