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Enteric Diseases

Despite WHO recommendations that all the world’s children should receive a rotavirus vaccine, today still over 77 million children do not have access to a rotavirus vaccine.  

The development of a novel human neonatal oral rotavirus vaccine (RV3-BB) is the culmination of over four decades of research in Australia by the Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne and the University of Melbourne, following the discovery of rotavirus by the team led by Professor Ruth Bishop in 1973.

The aim is to develop a safe, effective and affordable vaccine to protect babies from severe rotavirus disease from birth.  RV3-BB vaccine has now been studied in adults, children, infants and newborns in trials conducted in Australia, New Zealand, Indonesia and Malawi, Africa. RV3-BB vaccine has been shown to be safe and produce a good immune response in babies and infants – the target population. In Indonesia, where rotavirus causes over 8,000 deaths per year in children less than 5 years of age, our clinical trial showed that RV3-BB vaccine protected 95% of babies from severe rotavirus gastroenteritis in the first year of life and 75% of infants up to 18 months of age. This suggests that RV3-BB vaccine could have a significant impact if introduced in the routine immunisation program.  As a novel neonatal rotavirus vaccine delivered from birth, RV3-BB vaccine has the potential to address some the key barriers to effective rotavirus immunisation and improve safety and protection offered by a rotavirus vaccine.  Any inquiries regarding licensing RV3-BB vaccine should be directed to MCRI Business Development (jonathon.morison@mcri.edu.au). 

The Enteric Disease group hosts the WHO Collaborating Centre for Child Health, the WHO Rotavirus Regional Reference Laboratory for the Western-Pacific Region and the Australian Rotavirus Surveillance Program. 

Research activities of the group also includes understanding the reasons why some oral rotavirus vaccines do not provide good protection in infants in Africa and Asia, identifying and characterising strains of rotavirus circulating across Australia in children with gastroenteritis to ensure the ongoing effectiveness of the Australian rotavirus vaccine program and more recently exploring the role of gut infection by SARS-CoV-2 in transmission of COVID-19 in children and their families. 

Group Leaders: 
Group Members: 
Prof Ruth Bishop
Role: 
Esteemed Honorary Fellow
Prof Graeme Barnes
Role: 
Senior Principal Research Fellow
A/ Prof Carl Kirkwood
Role: 
Honorary Fellow
Amanda Handley
Role: 
Project Manager
Nada Bogdanovic-Sakran
Role: 
Research Assistant
Dan Pavlic
Role: 
Research Assistant
Susie Roczo-Farkas
Role: 
Research Assistant
Sarah Thomas
Role: 
Research Assistant
Huy Tran
Role: 
Research Assistant
Dr Celeste Donato
Role: 
Senior Research Officer
Emma Watts
Role: 
Clinical Project Manager
Fran Justice
Role: 
Clinical Trials Assistant
Christine Storey
Role: 
Administrative Associate
Darren Suryawijaya
Role: 
Research Assistant
Jane Standish
Role: 
Honorary Fellow
Dr Margie Danchin
Role: 
Honorary Fellow

Development of the novel human neonatal Rotavirus vaccine (RV3-BB)
RV3-BB vaccine was developed from the human neonatal rotavirus strain, RV3 (G3P[6]), identified in the stool of asymptomatic infants in Melbourne hospital nurseries in 1974-83.  Wild-type infection with RV3 provided protection from severe (100%) and moderately severe (75%) rotavirus gastroenteritis during the first 3 years of life with strong heterotypic serological responses to community rotavirus strains. Based on a human neonatal P[6] rotavirus strain, RV3-BB vaccine has intrinsic characteristics that may enhance its uptake in newborns and be more effective in populations of Africa and Asia with a higher prevalence of the Lewis negative phenotype. RV3-BB vaccine has now been studied in adults, children, infants and newborns in trials conducted in Australia, New Zealand, Indonesia and Malawi, Africa.  RV3-BB vaccine has been shown to be safe, immunogenic and be highly protective against severe rotavirus disease in babies and infants. In Indonesia, where rotavirus causes over 8,000 deaths per year in children less than 5 years of age, our clinical trial showed that RV3-BB vaccine protected 95% of babies from severe rotavirus gastroenteritis in the first year of life and 75% of infants up to 18 months of age.  The Enteric Disease Group have assisted in the development of a large scale manufacture process and formulation development with partners. The group has provided input to the RV3-BB vaccine program at BioFarma Indonesia. 

Exploring the barriers to oral rotavirus vaccine performance in low resource settings
Current licensed rotavirus vaccines provide less protection against severe rotavirus disease in infants in low income countries compared with that observed in high income countries, such as Australia. There have been many theories proposed to why this may occur.  Embedded within the clinical trials of RV3-BB we have included studies that explore the impact of maternal immunity and breast milk antibodies on vaccine take. We are also exploring the role of the gut microbiome, histo-blood antigens, co-administration of other vaccines such as oral polio vaccine and the developing immune responses in babies.

Australian Rotavirus Surveillance Program
The Australian National Rotavirus Reference Centre undertakes surveillance and characterisation of rotavirus strains causing severe diarrhoea in children and adults throughout Australia. This program undertakes molecular epidemiological studies on the rotavirus strains circulating in the population, which allows researchers to track seasonal changes in rotavirus strains causing severe disease.
Specific projects include:
•    Annual rotavirus surveillance of genotypes circulating in Australian children and adults with gastroenteritis.
•    Genetic characterisation of rotavirus strains emerging in the vaccine era.
•    Evolutionary analysis of strains to investigate selective pressures on strains circulating in the vaccine era.

WHO International Rotavirus Surveillance
The WHO Regional Reference Laboratory situated at MCRI supports Government and Reference Laboratories in the Western-Pacific region in the laboratory diagnosis of rotavirus infection.  
Specific projects include:
•    The Laboratory participates in the WHO annual proficiency testing, quality control program and the inter-regional quality control program.  Support is provided to national network laboratories in addressing laboratory problems and participates in training of national laboratory staff. 
•    Surveillance of rotavirus genotypes in the Western Pacific region

COVID-19
The Laboratory is involved in a range of projects through the COVID-19 at The Melbourne Children’s Campus project aimed to gain insights into how SARS-CoV-2 transmits, infects and causes disease in children. 
Specific projects include: 
•    SARS-CoV-2 testing of urine and stool samples collected through the FFX family transmission study 
•    Full genome sequencing and phylogenetic analysis of SARS-CoV-2 positive samples 

Funding: 

•    Bill and Melinda Gates Foundation
•    World Health Organisation
•    Department of Health and Aging, Australian Government
•    GlaxoSmithKline
•    Australian National Health and Medical Research Council 
•    CDC Foundation 

Collaborations: 

•    Bill and Melinda Gates Foundation
•    World Health Organisation  
•    PT Bio Farma Ltd, Indonesia
•    University of Melbourne
•    Malawi Liverpool Wellcome Trust
•    University of Liverpool,  UK
•    Universitas of Gadjah Mada, Indonesia
•    Menzies School of Health Research, Northern Territory, Australia
•    University of Otago, Dunedin, New Zealand
•    Monash University
•    London School of Tropical Medicine and Health