A brief history of MCRI

Newborn vaccine set to save lives

The award-winning team behind an affordable and effective gastro vaccine is ensuring it will save as many newborn lives as possible globally.

Long before COVID-19 vaccines became the focus of many of our conversations, Melbourne scientists laid the groundwork to protect infants against a common and potentially deadly form of dehydrating diarrhoea. After more than 50 years of hard work, the team has reached another critical milestone in vaccinating babies in emerging countries – and globally – against rotavirus gastroenteritis. It all began in 1973, when Professor Ruth Bishop, Professor Ian Holmes and their Melbourne team discovered rotavirus, leading to critical Murdoch Children’s research to better understand it. The discovery has so far inspired four oral rotavirus vaccines administered to babies from six weeks of age, which have saved countless lives in more than 100 countries, including Australia. Global Vaccine Action Plan data shows that from 2011-2020, up to 900,000 deaths were prevented. Murdoch Children’s Research Institute Enteric Diseases Group and RV3 Rotavirus Vaccine Program leader, University of Melbourne’s Professor Julie Bines and her team are now collaborating internationally to ensure that even more children are protected. Their latest research in Malawi has helped pave the way for what could be a highly effective vaccine for many thousands of babies across Africa and low-middle income countries globally.

Inspiring life-saving vaccines

After discovering a strain of rotavirus in the late 1980s that didn’t make babies sick, Murdoch Children’s researchers used it to develop the oral RV3-BB vaccine, which can be administered at birth. This has many benefits. Birth is a good time for health services to access mother and baby, and research has shown that the newborn’s microbiome is immature and may present less of a barrier. “Newborn babies haven’t developed their gut microbiome,” Professor Bines explained. “There seems to be not as much of a challenge to the vaccine at that time.” Current rotavirus vaccines can only be given at six weeks, but providing protection from birth could save many more lives.

Trials show promise

Clinical trials for RV3-BB, which was named after Professor Bishop and colleague Professor Graeme Barnes, have been completed in Australia, New Zealand, Indonesia and now Malawi. After years of rigorous research in collaboration with Universitas Gadjah Mada and Indonesian Government manufacturer BioFarma, which has developed a halal vaccine to reflect local preferences, there are now plans to introduce the vaccine into the Indonesian National Immunisation Program in 2023. But a major challenge that existing rotavirus vaccines have faced is uneven effectiveness in some parts of the world. They appear to be less effective in South Asian and African populations than in European populations, possibly due to variations in blood types. Professor Bines’ team has previously shown that the RV3-BB vaccine produces an immune response regardless of blood type so it may have an advantage in these high-risk populations.

New hope for African newborns

The latest research shows that RV3-BB is safe and produces a robust immune response in African infants.

Just published in Lancet Infectious Diseases, the phase 2 clinical trial conducted with the University of Liverpool found a reduced dose of RV3-BB produced the same immune response as a higher dose. Professor Bines co-led the study with University of Liverpool Medical Microbiology Professor Nigel Cunliffe. Their teams assessed the safety and immune reaction to three different amounts of the RV3-BB vaccine in 711 Malawian infants at birth or in their first weeks of life (trial participants, pictured left). The mid-dose performed as well as the higher dose, providing an opportunity to reduce the cost of manufacturing the vaccine, making it more affordable. “It’s safe for newborn babies and it produces an immune response in babies in Africa,” Professor Bines said. “It should be a costeffective vaccine.”

Helping those who need it most

Globally, rotaviruses still kill around 215,000 children aged under five each year, down from about 800,000 pre-vaccines. Many hospital stays have also been prevented. “The vaccines have made a major difference,” Professor Bines said, adding that improved hygiene and other advances had also played a role. The World Health Organization recommends all children receive a rotavirus vaccine, but millions still miss out. Murdoch Children’s is working with manufacturers to make the RV3-BB vaccine more affordable and accessible in African and Asian countries where vaccines can be cost-prohibitive. For example, PT BioFarma is conducting a phase 3 clinical trial of the halal RV3-BB vaccine in Indonesia, with results due in 2023. “Working with different manufacturers also provides an opportunity to develop the most appropriate approach for their population,” Professor Bines said.

Eureka, she’s got it!

The work of Murdoch Children’s Professor Julie Bines (back row, second from right) has been recognised with an Australian Museum Eureka Prize for her contribution in leading the development of RV3-BB, a vaccine that can prevent rotavirus gastroenteritis from birth, potentially saving thousands of young lives. Professor Bines’ work on RV3-BB has been in making it a safe, effective and affordable newborn rotavirus vaccine, particularly accessible for those in developing countries where the standard vaccines offered to Australian infants and children can be cost-prohibitive. “Rotavirus continues to be a major cause of death in young children and infants around the world, particularly in the poorest countries of Africa and Asia,” noted Professor Bines. “We’re working with emerging country vaccine manufacturers to produce a safe, effective and affordable vaccine that has the potential to save many thousands of lives and prevent suffering in many more. “This award is a wonderful acknowledgment of the efforts by many over the last four decades – including inspiring clinicians such as Graeme Barnes, Don Cameron, Yati Soenarto, Jim Buttery and Margie Danchin, and scientists such as Ruth Bishop, Ian Holmes and Carl Kirkwood, and the many, many others who have contributed directly or indirectly to this body of work.” In addition to leading the RV3 Rotavirus Vaccine Program at MCRI, Professor Bines is the Victor and Loti Smorgon Professor in the Department of Paediatrics at the University of Melbourne. She is a paediatric gastroenterologist and Head of Clinical Nutrition and Intestinal Rehabilitation at The Royal Children’s Hospital. Australian Museum Eureka Prizes are awarded annually in recognition of organisations and individuals who have contributed to science and the understanding of science.

Hear how Julie’s new rotavirus vaccine can prevent this nasty virus from birth

Republished with permission from pursuit.unimelb.edu.au MCRI is a signatory to the ACFID Code of Conduct, which is a voluntary, self- regulatory sector code of good practice. As a signatory we are committed and fully adhere to the ACFID Code of Conduct, conducting our work with transparency, accountability and integrity.

VCGS: Helping Victorian families for over a generation

Victorian Clinical Genetics Services (VCGS) is a leading provider of prenatal, childhood and adult clinical genetics services. We’ve supported thousands of Victorian families across multiple generations with life-altering health information.

Who are we?

We are genetics pioneers and knowledge translators. We’re also proudly a not-forprofit and wholly owned subsidiary of Murdoch Children’s. Our gifted team of researchers, clinicians, genetic counsellors, medical scientists and support staff are dedicated to making genetics and genomics accessible to everyone. Our core objective is to improve the lifelong health of children, individuals and families.

People are at the heart of everything we do

We believe that clinical genetics, genetic testing and genetic research are paramount to improving the health and wellbeing of children, individuals and families all over the world. Our Co-founder, Professor David Danks, inspired this approach as a pioneer of clinical genetics and genetic research in Australia. His early work positioned genetics at the forefront of life-changing healthcare, championing its contribution to the betterment of society. For the past 35 years, VCGS has provided continuous service to our newest Victorians (newborn screening), to pregnant people seeking reassurance (prenatal screening), to worried parents looking for answers (childhood microarray and exomes), and to families touched by rare disease with nowhere else to turn (acute care genomics). We strive to make genetics more accessible, understandable and useful for all our patients – from preconception through to adulthood.

What do we do?

We support our newest citizens – 2.2 million babies screened and counting. VCGS, in partnership with the Victorian Department of Health, delivers the hugely successful newborn bloodspot screening program. As of 2021, the program has screened more than 2.2 million newborn babies. Screening began in 1966 in Victoria and enables the early identification and treatment of babies with serious and sometimes life-threatening medical conditions. Over time, the number of conditions screened has grown from one to 27, with plans for more to be added. Detecting these conditions and intervening early to improve outcomes makes a big difference to the health and wellbeing of babies and families.

We support new parents and parents to be

Becoming a parent is a special privilege and we’re incredibly lucky to share in that reproductive journey. Our tests provide information and reassurance about the chances of having a child with a genetic or chromosomal condition.

Pre-pregnancy screening

VCGS was first in Australia to introduce genetic carrier screening in 2013. These tests identify individuals who are carriers of three common inherited genetic conditions: cystic fibrosis, fragile X syndrome and spinal muscular atrophy. Those identified as carriers can then use modern medicine to have a child who will not inherit one of these serious, life-limiting conditions. We are now leading research to broaden carrier screening options so couples have access to even more information on their journey to parenthood.

Pregnancy screening

In 1996, we pioneered the use of maternal serum screening in Victoria. This was the gold standard in testing for Down syndrome during pregnancy. In recent years, we went a step further and developed an Australianbased, non-invasive prenatal test (percept NIPT), which gave Australians access to the latest reproductive technology. NIPT uses ‘cell-free DNA’ and is the most accurate screening test for Down syndrome. Significantly for pregnant people, NIPT reduces the need for risky, invasive procedures. To date, we’ve given close to 1 million pregnant people information about the health of their pregnancy. For those who receive unexpected news, our team of genetic counsellors offer one-to-one support and guidance in making decisions that are right for them and their families.

We support families with answers to complex questions

Over the past 35 years, knowledge about how our genetic make-up affects our health has continued to expand. Genetic testing at VCGS started with the study of whole chromosomes, the structures that carry our genetic information in the form of tightly packed DNA. These tests allowed us to identify the cause of several health and development problems. But many complex cases went unexplained. However, since completion of the Human Genome project in 2003, our understanding of genetics and the pace of technological development has exploded at VCGS. We’ve now moved from ‘genetics’, looking at single genes, to ‘genomics’, looking at all our genes, which gives us powerful new tools for investigating complex health problems. Incredibly, genomic testing can now provide answers for patients who have exhausted all other testing avenues. For critically ill babies in intensive care, such testing can provide answers in as little as three days. This means fewer hospital days, fewer invasive procedures, a definitive diagnosis and, for some, access to life-saving treatment. Being able to make a genetic diagnosis provides invaluable comfort and clarity for families and offers a path forward. Genomic testing also has the potential to end the relentless diagnostic odyssey for thousands of families who bounce from service to service with unanswered questions.

We embrace the future of genomics and use it to improve lives

The future of genomics at VCGS and Murdoch Children’s is exciting. Associate Professor Sebastian Lunke believes that “as evidence of benefit grows, potentially every child from birth will have their DNA sequenced, setting them up for their best possible future. Critically ill children and their families searching for a diagnosis would have answers in hours, not days”. The future looks bright as we continue our work to make genomics universally accessible for lifelong health.

Cracking the genetic code

Genomics delivers rapid diagnosis and treatment

Children like Levi Trowbridge, who experienced his first seizure aged just three days, have a brighter future thanks to a new collaboration of world-leading genomics institutes. Murdoch Children’s Research Institute is part of the International Precision Child Health Partnership, or IPCHiP, which is improving the lives of children with complex genetic conditions. When Levi’s seizures began, he entered the care of Murdoch Children’s epilepsy team leader and the RCH paediatric neurologist Dr Katherine Howell. Levi had multiple seizures every day and at his weakest was on life support. Within days, rapid genomic testing diagnosed him with KCNQ2 epileptic encephalopathy, a rare genetic disorder. This enabled doctors to change his medication, which soon stopped the seizures. “Levi improved rapidly,” Dr Howell said. “His multiple daily seizures stopped by the time he was three weeks old; he was more alert, started to feed well and was able to go home from the hospital.” More children will benefit from earlier diagnosis and targeted treatment thanks to the partnership, which includes Murdoch Children’s (with The Royal Children’s Hospital and the University of Melbourne), The Hospital for Sick Children in Toronto, Boston Children’s Hospital, and London’s UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital. Their experts will better analyse medical and genomic data to rapidly diagnose serious childhood illnesses, plus find and develop improved, more personalised treatments. “With individual babies like Levi we’ve had a glimpse of the possible benefits of prompt genetic diagnosis, but we now want to understand how much benefit this approach might provide to all the infants we see with these devastating conditions,” Dr Howell said. More than 7,000 rare diseases affect millions of people around the world, but only a few hundred receive approved treatments. IPCHiP is the first major global collaboration around genomics and child health and its first project will involve severe infant epilepsy. Investigators will enrol babies diagnosed in their first year, sequence their genomes, change treatment based on the findings, and follow their development over the long term. Associate Professor Sebastian Lunke, the Head of Genetics and Genomics at Victorian Clinical Genetics Services, said another key early program of IPCHiP would be to improve acute care genomics. This would speed ultrarapid diagnosis and, hopefully, treatment for a range of neurological, metabolic, heart and other disorders. He hoped that IPCHiP would also eventually enable experts to predict future conditions. “The faster that we get an answer, the better the outcome for the child,” he said. Levi’s mum Karsha said the fast diagnosis was a godsend and the partnership would help many families globally. “By sharing resources and knowledge, researchers can test and tailor new treatments for children with rare conditions,” she said.

Advances in infectious disease

The pandemic shone a light on the importance of our immune systems in dealing with infection. Murdoch Children’s continued its critical work in this space in 2021, taking on COVID-19 and other pressing global infectious diseases.

Amid the urgent challenges, came some good news. Drawing on hospital data from Victoria’s Department of Health, researchers showed that COVID-19 precautions led to fewer children and teenagers receiving hospital treatment for other common respiratory infections. The research highlighted the potential of nondrug measures such as good hand hygiene, physical distancing, school and business closures, and travel and social restrictions in reducing the spread of infectious diseases. These simple public health measures, which helped contain COVID-19, were also likely to work against all types of infection. Infection-related hospital stays fell by 65 per cent in the seven months following the introduction of pandemic infection controls in 2020, compared with the previous five years.

Children with cancer

Murdoch Children’s research showed that children undergoing cancer treatment were still at relatively low risk of developing severe COVID-19 after becoming infected. But they were much more likely to have a severe case if they had underlying conditions such as acute co-infections and low white blood cell counts. The study by Murdoch Children’s, Peter MacCallum Cancer Centre and Goethe University looked at COVID-19 severity, shedding duration, symptoms and outcomes in 131 children with cancer in 10 countries including Australia. The group found 95 per cent of children with cancer fully recovered from COVID-19. A third (37 per cent) required hospital treatment, 11 per cent entered ICU and four died. Those with serious cases tended to have comorbidities, infections and/or compromised immune systems. Murdoch Children’s and Peter Mac’s Associate Professor Gabrielle Haeusler said while the study identified some predictors of severe illness, prevention was still the best defence. “Ongoing surveillance is also critical in monitoring vaccine efficacy and impact of emerging COVID-19 variants in this vulnerable population,” she said.

Cell-based flu vaccine

In a typical year, up to 15 per cent of the world’s population contracts influenza, leading to as many as 650,000 respiratoryrelated deaths. The cell-based flu vaccine production process is an alternative to the traditional manufacturing technique that requires fertilised hens’ eggs. Cell-based vaccine technology could potentially be more effective, and offer increased scalability and production speed. New research conducted with the Peter Doherty Institute for Infection and Immunity found a cell-based influenza vaccine can protect against the flu in children and adolescents. Led by Vaccine and Immunisation Research Group (VIRGo) head Professor Terry Nolan, the study found the cell-based quadrivalent influenza vaccine (QIVc) produced a sufficiently robust immune response in children aged 2-18. Published in The New England Journal of Medicine, it was the first study looking at responses in children as young as two.

Antibiotics in pregnancy

A Murdoch Children’s-led review found a common antibiotic, azithromycin, can reduce low birth weight and premature births if taken during pregnancy in countries with significant malaria cases. The systematic review found azithromycin reduced low birth weight and prematurity in Africa and Asia. But it didn’t lower infant deaths, infections, or hospital admissions. Azithromycin is inexpensive and widely used to treat chest and ear infections. It was unclear whether it would improve perinatal and neonatal outcomes in non-malaria endemic settings, and the potential harm on stillbirth rates needs more investigation. Similar research is underway in Fiji. Murdoch Children’s Professor Fiona Russell said all this research was likely to inform global maternal child health policy and, hopefully, benefit infants and mothers around the world.