Blazing a trail in antibody and immunity research

Using next generation technologies, Dr Deborah Burnett’s research at the Garvan Institute of Medical Research is tracking antibody responses in the area of protective immunity and autoimmune disease. In early 2020, when the COVID–19 pandemic hit, she pivoted her expertise to explore vaccination strategies to induce antibodies that the virus cannot escape. Deborah’s research in this area led to important discoveries which have redefined the role of antibodies in health and disease. Her research has been published in prestigious journals including Science, Immunity, Cell and Proceedings of the National Academy of Sciences.  

In 2022, Research Australia recognised Deborah’s trailblazing work with the Highly Commended Discovery Award. The same year she was awarded an RNA Future Leaders Grant from the NSW Health Office for Health and Medical Research. This grant supported work which has led to Deborah receiving a highly competitive five-year fellowship from the National Health and Medical Research Council, to commence in 2025. In 2023, she also received the NSW Premier’s Prize for Early Career Researcher of the Year (Biological Sciences) and the L’Oréal UNESCO For Women in Science Fellowship. Deborah currently co-leads collaborative initiatives that span research institutions and hospitals, with a focus on enhancing vaccine efficacy against challenging infectious threats including those linked to autoimmune diseases. 

What is your current title? 

Group Leader at the Garvan Institute of Medical Research 

Can you explain a little about the work you do with antibodies and vaccines and why it is so important? 

Antibodies are critical in protecting us against a variety of infectious diseases. My work aims to understand how best to assist the body in developing antibodies against important infectious threats. The end goal is to then use this knowledge to help advance vaccine design. In particular my work aims to generate improved pre-clinical models for vaccine evaluation. Pre-clinical models are systems we use to evaluate vaccines prior to testing them in humans during clinical trials. Developing cost-effective and accurate pre-clinical models is critical for vaccine development.  

Pre-clinical trials can save years and hundreds of millions of dollars by helping select correct vaccines to advance to the resource-intensive clinical phases. They are also important from a safety perspective to ensure we fully understand the effects of any vaccine before any impact on human health. We are developing new and improved pre-clinical models for vaccine development against challenging threats of infectious diseases which have evaded immune protection until now. For example, this work will help address infections such as Group A Streptococcus, bacteria which can mimic molecules on our own tissues, and which can lead to devastating autoimmune diseases like rheumatic heart disease; or infections such as SARS-CoV-2, which can easily mutate to evade our protective immune response, meaning that vaccine boosters need to be continually updated.  

What discoveries have you made in your work and how are they being applied to healthcare, improving vaccines and patient outcomes? 

In my work I’ve been involved in several discoveries which have advanced the field of vaccine development. In one discovery we found that self-reactive B cells, found naturally in the human body, can be safely recruited into the immune response against infections which mimic our own molecules. This means they can help the immune system defend the body against certain infections that can be difficult to prevent or treat. Our discovery has since been adapted by teams around the world and used in developing vaccines against threats which mimic our own tissues, for example HIV and cancer. 

I have also been involved in developing a model system to evaluate COVID-19 vaccines for their capacity to generate protective immunity against key elements of the virus that are resistant to mutational escape, which is the process where viruses evolve genetic mutations. This allows them to evade the protection provided by our existing antibody defences. This process is the reason that emerging viral variants can expand into ongoing waves of infection even in people who have already developed immunity through either natural infection or vaccination against previous strains. We are now testing a range of clinical and pre-clinical vaccines from across Australia to better determine their capability for providing enhanced protective immune responses.  

What applications do you hope your work will have in the future?  

My work is now focusing on developing improved pre-clinical models that better correlate with the human immune response. This is critical as currently more than 90% of vaccines fail only in the later phases of clinical evaluation which is exponentially more time consuming and expensive. Pre-clinical evaluation is needed to rapidly, accurately and safely triage and “fast-fail” or “fast-pivot” vaccine candidates prior to clinical evaluation in humans. Improved pre-clinical evaluation has the potential to save years and hundreds of millions of dollars per vaccine candidate. This work will become increasingly important to match the advancements in mRNA and viral vector technologies that we now use to design and produce new vaccines. These technologies have enabled cheaper and faster development of a much larger number of vaccine candidates. Developments in the area I am working in will help ensure that we have the capacity in Australia to accurately select which vaccines to advance for these resource-intensive downstream clinical phases.  

What drew you to work in the area of vaccine research? 

Before 2020, my primary area of focus was exploring B cells in autoimmune diseases. Then the COVID-19 pandemic led to a critical pivot point in my research career, when in early 2020, it became apparent the COVID-19 pandemic was like nothing we had seen in our lifetime and Australian researchers needed to adopt new strategies to ensure we could make meaningful discoveries as quickly as possible to influence health outcomes. It quickly became clear that the skills I had developed, using novel tests called assays to trace B cells and antibody responses to specific targets, could be of use for exploring vaccine responses to COVID-19.  

 With the COVID-19 pandemic we realised the extraordinary and rapid advancements that could be made by different teams across NSW working together, each sharing their resources and expertise across the sector. The collaborative networks we formed at that time made extraordinary advancements that were directly referenced by the US based Centers for Disease Control and Prevention and the Australian Technical Advisory Group on Immunisation. They also directly influenced public vaccine advice and vaccine development strategies. We’ve continued those initiatives through ongoing work within the community to establish collaborative academic networks within NSW which work together to share advice and resources for vaccine development.  

 What kind of study have you completed to qualify for your work? 

My initial training was in Veterinary Science and I worked as a vet in Australia and New Zealand. Although I loved working with and treating animals, I became frustrated by the questions that remained unanswered as to why some treatments worked so much better in some cases than in others. This compelled me to transition into a career in medical research. Having this unusual background and deeper understanding of comparative biology, has been very useful in my current work in vaccinology and immunology.  

 I undertook my honours study at the Walter and Eliza Hall Institute in Melbourne, looking at factors that affect platelet survival and activity. I then completed my PhD in Sydney at Garvan exploring B cells that cross-react to our own tissues. In 2022 as a Group Leader at Garvan, I was awarded a NSW Health RNA Future Leaders Grant. The NHMRC Investigator Grant I was recently awarded which will begin in 2025, will allow me to establish my own laboratory at UNSW to develop sophisticated improved pre-clinical models to assess vaccine responses. I hope that one day the discoveries we make in relation to understanding antibody responses to mRNA vaccines and other vaccine types will not only be useful for human medicine but can also be applied across the “One Health” spectrum to help solve questions about animal diseases.  

 Could you name some of the most rewarding aspects of your work?  

Science is full of highs and lows. At times it can be incredibly frustrating when you don’t obtain the research results you were expecting or a scientific problem takes longer to solve than you anticipated. But the key to a rewarding career in medical research is keeping an open mind for new and unexpected findings. There is no feeling in the world like knowing that you’ve just discovered something important for human health and that at this point in time, your team is the first in the world to have uncovered this breakthrough. Having the opportunity to then share that discovery with the world and watch others in the field implement your finding in their own research is beyond rewarding and exciting.  

 What are the biggest challenges in your work? 

One of the hardest challenges in science is the long timelines required to fully clarify and validate a discovery. It may take years between formulating a hypothesis and performing the critical experiments to test your theory. More years may follow between making your discovery and validating it sufficiently to share the work publicly. Then it may take more years as you study the real-world clinical impact that discovery can have on human health. So, you need to have endurance and patience! 

Could you briefly describe a career highlight? 

Receiving the award for the NSW Early Career Researcher of the Year (Biological Sciences) in December 2023 was a real high point for me. Other highlights have come from invitations to give presentations about topics I’m passionate about. The first of these occurred last year when the team from the Office for Health and Medical Research invited me to speak about NSW collaborative biopreparenedess strategies at BIO, the world’s largest life sciences conference. It was an exhilarating, humbling and incredible learning experience, to be involved in establishing collaborative vaccine evaluation networks amongst scientists and across academia, industry and government. A second presentation highlight took place earlier this year when I was invited to join a panel of speakers at the Ausbiotech Women in Lifesciences Luncheon discussing the barriers and opportunities for Women and Gender Diverse individuals in the life sciences sector.  

Can you describe what different tasks a day in your role might involve?  

Every day in science is a different set of adventures and challenges! I spend some days in the lab trying to recognise and isolate antibodies and better understand their role in fighting infectious threats. Other days I’ll be supporting my team, helping students design their own experiments or present their results. Another favourite part of my job is taking the opportunity to share our discoveries. In addition to sharing our research through publications and scientific presentations, we also share our work through collaborative research networks. This allows us to take advantage of the unique knowledge and skills of the many research and industry teams across Australia so that together, we can enhance the progress and quality of our research.  

Why is the work you do so important for the future health of Australians? 

While treating diseases is of critical importance, eliminating diseases entirely, as historically occurred through the effective vaccine campaigns against smallpox or polio, is the only path forward to create a fair and equitable future for humanity. Vaccine research is becoming more critical in our society as we adapt to a world with global connectivity, climate change and novel human and animal interactions. This status quo has made emerging diseases such as novel coronavirus outbreaks more likely, and re-emerging diseases such as dengue fever, more common. This challenge becomes even more important as we enter an age where previous drug therapies like antibiotics become less effective and we need to ensure that medical research keeps pace with the development of these evolving threats.  

What grant did you receive from the Office for Health and Medical Research, for your work?  

The Office has been wonderful in supporting my research and career development. I am immensely grateful for the advice, guidance and promotion the people at the Office have provided for me and for our team, in establishing several collaborative vaccine initiatives. In 2022, I received an NSW Health RNA Future Leaders Grant through the Office for Health and Medical Research. This is being used to develop a COVID-19 mRNA vaccine resistant to mutational escape. We hope that this vaccine will protect more effectively against current COVID-19 variants and future variants that have not yet developed. This means that rather than retrospectively rolling out updated booster vaccines with each new variant, this style of vaccine could be rolled out prospectively, possibly providing protective immunity in the population before those variants even arise. This work has led to a critical turning point in my career and career trajectory and has been fundamental to me going on to also receive my recent grant from the National Health and Medical Research Council.  

The Office has also furthered collaborative vaccine development through a collaborative COVID-19 Vaccine Accelerator Grant. Their ongoing support in this space has helped to ensure that vaccine efforts in NSW best capitalise on the wealth of unique skills and resources that exist within NSW’s vaccine development pipeline.