Head of the Molecular Virology Laboratory in the Department of Microbiology and Immunology, University of Melbourne
The Doherty Institute for Infection and Immunity, Australia
What are you and your institution currently working on regarding COVID-19?
Over the past two winter months, Melbourne has experienced a second wave COVID-19 outbreak more severe than the first in our late summer and the Doherty Institute has led the diagnostics and paired this with deep SARS-CoV-2 genomics analysis and immune profiling. While the first outbreak resulted from numerous point source ignitions from returned travelers with wide viral diversity, the recent outbreak showed rapid community spread that featured a more limited viral diversity including strains with a curious assembly of mutations, especially in the virus Spike. While the Doherty viral genomics team have contributed 5% of the worlds full genome sequences, we have 78% of all annotated receptor binding domain (RBD) mutants. My role as the Doherty Institute virology theme leader helped draw together a wide collaborative effort to ensure we isolated these virus strains from diagnostic samples to study their replicative fitness and their susceptibility to antibody.
Please describe your clinical isolates work, and the role your local Spike mutant strains play in assessment of vaccine-induced antibody and mAbs.
One highlight has been the isolation of a virus strain from a now extinguished small cluster that had a Spike RBD mutation originally observed in a distinct mouse adapted strain in China. Our clinical isolate was capable of immediately replicating to high infectious titers in normal laboratory mice and now provides an important new tool for larger scale animal testing of antiviral drugs and vaccines. Of particular interest is the neutralisation efficacy assessment of antibody induced by Australian vaccine candidates and of locally produced monoclonal antibodies against several of the efficient transmitting Spike RBD mutant strains in local circulation. We are finding that the small evolutionary steps made by the virus can lead to important phenotypic outcomes for replication and antibody sensitivity. Our Institutional experience in the testing HIV and Influenza vaccines and therapies has primed us to expect that viral genetic diversity, even at the low levels seen with this slow mutating coronavirus, can be important when confronting an expanding outbreak. Monitoring and assessment of these RBD mutant strains is ongoing. But importantly, the potential efficacy of antibody powered preventions in our setting now include testing for their breadth of activity against these common local mutant strains. We are now considering the powerful role viral genomics could play beyond epidemiological surveillance, in monitoring the efficacy and escape from antiviral drugs and vaccines.
Professor Damian Purcell is head of the molecular virology laboratory in the Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity at The University of Melbourne. After receiving a PhD from the University of Melbourne in 1987 he was a CJ Martin traveling fellow with Dr. Malcolm Martin at the Laboratory for Molecular Microbiology of the NIAID, at the NIH in Bethesda, Maryland. He returned to Melbourne’s Burnet Institute in 1995 before moving to a tenured teaching and research position at The University of Melbourne in 2001. He is the Virology Division Chair for the Australian Society of Microbiology, the immediate past President of the Australasian Virology Society, and Executive member of the Australian Center for HIV and Hepatitis Virology. He studies RNA-mediated control of retrovirus gene expression during productive and the latent phase of infection. He seeks to translate his insights into the molecular mechanisms governing viral replication and the innate and adaptive antiviral responses into new antiviral drugs, vaccines and biomedical preventions.
About the Doherty Institute for Infection and Immunity
Finding solutions to prevent, treat and cure infectious diseases and understanding the complexities of microbes and the immune system requires innovative approaches and concentrated effort. This is why the University of Melbourne – a world leader in education, teaching and research excellence – and The Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, research and learning – partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally.
Located in the heart of Melbourne’s Biomedical Precinct, the Doherty Institute is named in honor of Patron, Laureate Professor Peter Doherty, winner of the 1996 Nobel Prize in Physiology or Medicine for discovering how the immune system recognizes virus-infected cells. Under the expert guidance of Director, University of Melbourne Professor Sharon Lewin, a leader in research and clinical management of HIV and infectious diseases, the Doherty Institute has more than 700 staff who work on infection and immunity through a broad spectrum of activities. This includes discovery research; diagnosis, surveillance and investigation of infectious disease outbreaks; and the development of ways to prevent, treat and eliminate infectious diseases.