The Doherty Institute’s extraordinary year of COVID-19

THE Peter Doherty Institute for Infection and Immunity (Doherty Institute) became a household name in Australia in 2020. Expertly led by infectious diseases physician and basic scientist, Director Professor Sharon Lewin, it was a key contributor to the evidence base underpinning public health intelligence and strategy, best practice clinical care, and discovery science supporting local, national and regional responses to COVID-19.

Doherty Institute scientists and public health staff, including our notable namesake, became trusted experts on our screens, on the radio and in newspapers, discussing the latest evidence and giving sound public health advice.

The pandemic has been a defining event for the Doherty Institute and a clear justification for the vision that underpinned its conception. It was intended to be an enabling ecosystem where research, education and public health activities could fruitfully combine to provide a resource for health and policy decision makers during infectious diseases threats. Having just celebrated its fifth birthday in September 2019, the Institute was called upon to fulfil this role in 2020. Some of the year’s highlights are detailed below, representing the work of many teams who pivoted to focus on this new threat.

Dr Mike Catton and Dr Julian Druce achieved a place on the global stage in January 2020 as the first people to isolate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside China and they moved rapidly to share the virus with researchers and public health institutes around the world.

The Doherty Institute Public Health laboratories played a key role in supporting the testing effort throughout the pandemic. Contributions included development and validation of innovative approaches using less invasive methods such as saliva for repeated surveillance screening, through research led by Professor Deborah Williamson and Professor Ben Howden, along with Dr Mike Catton and others.

Professor Ben Howden and colleagues have played a key role in national networks characterising virus genomics and have helped Victoria to achieve one of the highest rates of sequencing of COVID-19 cases globally. This work has enabled ongoing analysis of the landscape of SARS-CoV-2 variants arriving in Australia, supporting international genomic surveillance efforts, as well as providing critical intelligence for local outbreak responses. Diagnostic and sequencing support has also been provided to countries in our region.

Professor Kanta Subbarao, Director of the Doherty Institute’s World Health Organization Collaborating Centre for Reference and Research on Influenza (WHOCCRI), leveraged her significant expertise in coronaviruses to play a pivotal international role in development of neutralisation assays and methods. Professor Patrick Reading, Senior Medical Scientist and Educator in the Centre, worked through existing WHO training networks to support development of regional laboratory capacity across the Indo-Pacific region.

Professor Jodie McVernon and University of Melbourne colleagues have led a collaborative, nationally distributed modelling network informing the Commonwealth strategic response to COVID-19 since January 2020. Model-based advice has included ongoing weekly situational assessment for key national policy committees using harmonised approaches based on behavioural, mobility and epidemiological data across all states and territories.

This work has informed escalation or easing of public health and social measures and contributed to a detailed evaluation of non-pharmaceutical interventions coordinated by the WHO. With support from the Department of Foreign Affairs and Trade (DFAT), the modelling team have worked with the Walter and Eliza Hall Institute, the Burnet Institute, the WHO and country partners to support regional preparedness, situational assessment and response in many Indo-Pacific countries, including Papua New Guinea and French Polynesia.

The Victorian Infectious Diseases Service, led by Professors Kirsty Buising and James McCarthy, ensured that the Royal Melbourne Hospital (RMH) played a leading role in caring for Victorians with COVID-19. This remit included clinical and infection prevention support for the residents of local housing towers placed into hard lockdown early in Victoria’s second wave in July 2020. The Doherty Institute also supported infection prevention and control training in Papua New Guinea through existing programs funded by the DFAT.

Faced with rising COVID-19 cases in RMH health care workers, a multidisciplinary response substantially strengthened hospital infection control measures, establishing new standards that were adopted throughout Victoria and other Australian jurisdictions. Innovative and effective approaches developed included testing of “air scrubbers” to reduce airborne transmission of SARS-CoV-2.

As a new disease, little is known about what treatments may be effective for patients with COVID-19. Associate Professor Steven Tong and collaborators from across Australia and New Zealand and, most recently, India started the AustralaSian COVID-19 Trial (ASCOT), which aims to discover which treatments are most effective in patients hospitalised with COVID-19 and whether they will prevent patients deteriorating to the point of needing a ventilator in the intensive care unit. The trial has been largely funded by the generous support of philanthropists.

Professors Sharon Lewin and Jodie McVernon have played leadership roles in the National Health and Medical Research Council-funded Australian Partnership for Preparedness Research in Infectious Disease Emergencies (APPRISE). This national interdisciplinary network was established in 2017 to undertake and coordinate clinical, laboratory and public health research relevant to pandemic preparedness and response. APPRISE received additional government and philanthropic funding in 2020 to enable research platforms and projects across all relevant domains. A unique First Nations-led funding call supported 11 projects that will result in better outcomes for First Nations communities.

The Doherty Institute’s strengths in virology have helped to establish new model systems for the study of SARS-CoV-2. Professor Damian Purcell was central to identifying and encouraging a variation in the genetic sequence enabling mice to be infected with the virus. Professor Kanta Subbarao and Professor Elizabeth Vincan have collaborated with the Murdoch Children’s Research Institute and Monash Health to establish a tissue model derived from adult stem cells to better understand how COVID-19 infections progress in human cells. Professor Sharon Lewin and Dr Wei Zhao have worked with cancer specialists at the Victorian Comprehensive Cancer Centre to evaluate CRISPR-Cas13 as a novel therapeutic solution for COVID-19.

The impact of the COVID-19 pandemic on the wellbeing of Victorian adults, along with community awareness and attitudes towards the government’s COVID-19 policies and directions throughout 2020 and into 2021, are being elucidated in the Optimise Study – co-led by Dr Katherine Gibney in partnership with the Burnet Institute.

The Doherty Institute has also been a leader in characterising immune responses to COVID-19. Professor Katherine Kedzierska, Dr Oanh Nguyen and colleagues have systematically mapped antibodies developed in response to SARS-CoV-2, gaining insights into why some people develop severe disease. Professor Stephen Kent, Dr Jennifer Juno and others described the evolution of these antibody levels up to 4 months following COVID-19 infection, showing a sharp decrease over the first 1–2 months that then slows down. These findings were compared with other “common cold” coronaviruses, guiding future studies of respiratory virus immunity and vaccine responses.

With funding support from the Medical Research Future Fund, Professor Dale Godfrey and Professor Terry Nolan are working on a COVID-19 vaccine candidate in collaboration with the Monash Institute of Pharmaceutical Sciences and Seqirus. Following encouraging pre-clinical testing it is hoped that this candidate will progress to human phase 1 clinical trials in late 2021.

The extent of our work to date would not have been possible without the generous support of philanthropists, the Victorian State Government, the Commonwealth Government and our collaborators.

What roles will the Doherty Institute play over the coming year?

Vaccine roll-out over the course of 2021 will enable our next transition to a new phase of “COVID-19-normal” associated with easing of public health and social measures and a pathway to increased global connectedness. Through this phase we will continue our contributions to diagnosis, clinical care and public health efforts.

“Known unknowns” over the course of the next year include the degree and durability of vaccine protection, particularly against emerging SARS-CoV-2 variants, prompting Doherty Institute researchers, with others, to continue the search for newer vaccines and therapeutics. An ongoing process of adaptation, innovation and preparation is essential to be ready for the next challenge that SARS-CoV-2 or “disease X” presents. In the words of Louis Pasteur, “Fortune favours the prepared mind”.

University of Melbourne Professor Jodie McVernon, Director of Doherty Epidemiology, is a public health physician and epidemiologist with extensive expertise in clinical vaccine trials, epidemiologic studies and mathematical modelling of infectious diseases to inform policy.

The Royal Melbourne Hospital’s Dr Katherine Gibney is an infectious diseases physician, public health physician and medical epidemiologist at the Doherty Institute. She has a particular interest in infections in immigrants and returned travellers, vector-borne diseases, gastrointestinal infections and Indigenous health.

The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.