The whole HKU-Pasteur team wishes to congratulate Dr Máiréid Bull!
She has successfully defended her PhD thesis, under the supervision of Sophie Valkenburg and Leo Poon, on T cell immune pressure Influenza Virus genome within a universal vaccination model. A good occasion to ask her a few questions about the 5 years she has spent here with us in Sophie's team.
HKU-Pasteur Research Pole: Can you tell us about yourself in a few sentences?
Máiréid Bull: I came to Hong Kong and joined HKU-Pasteur Research Pole in 2016 and I am now a PhD graduate from Dr Sophie Valkenburg’s team.
I myself am Irish/British but born in Zimbabwe. My family moved around a lot when I was younger and I was lucky to have the chance to grow up in a lot of different countries like Jamaica and Nepal. I have absolutely loved studying and living in Hong Kong, it’s been a great adventure!
HKU-PRP: Can you describe your professional path so far and why you choose to engage in a scientific career? MB: I’ve always loved Biology from a young age but in my final years of secondary school, a close friend lost her father to cancer. Seeing the pain her and her family went through made me want to go into medical research with a hope to being able to contribute to the improvement of human health. This interest led me to pursue a BSc in Immunology at the University of Glasgow where I developed an interest in infectious diseases and to explore this further undertook an MSc in Immunology of Infectious Diseases at the London School of Hygiene and Tropical Medicine. HKU-PRP: What is the title of you PhD thesis and why did you choose this topic? MB: My PhD thesis was titled “Investigation of T cell Immune Pressure on the Influenza Virus Genome within a Universal Vaccination Model”. I found it to be an exciting research area with potential for real-world implications and could build upon the previous work done by my supervisor Dr Sophie Valkenburg so it was a great opportunity. Next generation universal influenza vaccines are fast becoming a reality so it’s important to investigate how they might further interact with our immune system so we can inform future vaccine design. HKU-PRP: What is/was the most challenging? MB: My project required a lot of troubleshooting as it was a novel approach to a novel question. And I think the hardest thing about this was keeping up morale, but failure can also be a great teacher. It’s a phase that most PhD students go through and after a lot of persistent effort things will work out in the end. HKU-PRP: Any advice you would like to share for future PhD students? MB: Building a support network is really important. I was lucky to have two very supportive supervisors, but it was also important to support my fellow students and in turn receive support from them. HKU-PRP: You have spent 5 years in HKU-Pasteur now. What is it that you particularly like about this place, in and outside the lab, that you will take with you? MB: I think my favourite thing about HKU-Pasteur is the sense of community. Even though we are multiple teams working in very diverse areas, we all feel connected as Pasteurians. I would hope to contribute to that sense of community in research groups I join in the future, while maintaining the connections I have made here. HKU-PRP: What is the next step for you now? MB: I will be heading back to the UK to be closer to family and joining University of Oxford as a Postdoctoral Immunologist, where I will be assisting with the ongoing COVID-19 vaccine research. HKU-PRP: Thank you Máiréid, and we wish you all the best for your next adventure back in UK! Abstract of the thesis: Investigation of T cell Immune Pressure on the Influenza Genome within a Universal Vaccination Model Improved vaccination strategies are needed against influenza which affects millions of people annually and causes a substantial health burden in many countries. Current strategies are vulnerable to seasonal adaptations caused by mutations within the influenza genome which are generated in response to selection pressure and offer little to no protection against newly emerging pandemic influenza strains. Next generation vaccines aim to provide universal protection against current circulating viruses and future arising variants. Universal vaccination can be achieved through multiple approaches, but a prevailing theory is augmenting T cell responses to leverage T cell recognition of conserved viral epitopes of influenza viruses. While T cells are essential for viral clearance and reducing severity during influenza infection, they can also exert increased immunological pressure which can lead to viral variants which adapt to circumvent the immune response. The capacity of T cell-activating vaccines to inadvertently cause viral escape mutants is one of the biggest questions still facing next generation vaccine design. This study characterises mutational rates of the influenza genome and immunological responses to a next generation vaccine, Wyeth/IL-15/5Flu within a mouse challenge model. It was observed that this universal vaccine candidate leads to an increased incidence and frequency of significant mutations across multiple influenza genes when compared to mock vaccinated or seasonal inactivated influenza vaccines. However, the nature of these mutations appears to be stochastic, as few variants arose directly within T cell epitope regions. No high frequency T cell escape mutants were identified during this study, but potentially beneficial mutations were seen to arise in non-epitope regions after Wyeth/IL-15/5Flu vaccination, such as in polymerase genes and HA glycosylation positions. T cell depletion of Wyeth/IL-15/5Flu vaccinated mice reduced the incidence of significant mutations and the overall mutational frequency across multiple genes, indicating that this increased mutational rate is T cell mediated. This suggests that universal influenza vaccination may provide an increased opportunity for adaptations to arise within the influenza genome. This study also further characterised effects of mild immunopathology of increased weight loss associated with universal vaccination. Wyeth/IL-15/5Flu vaccination skewed the response to an inflammatory Th1 response compared to an anti-inflammatory Th2 response upon group 2 virus challenge. It is possible this occurred due to a mismatch between humoral group 1 influenza-specific vaccine immunity and heterosubtypic cellular immunity during group 2 influenza infection. This study provides a novel examination of the effects of next generation T cell-activating vaccines on the influenza genome and host responses. This project used an interdisciplinary approach combining both next generation sequencing techniques and immunological approaches to determine the impact of universal vaccination against the influenza genome. These findings can help inform future vaccine design and aid in the generation of improved influenza vaccination strategies.