Enteric Diseases

To reduce disease burden and deaths due to enteric diseases.

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 of the key barriers to effective rotavirus immunisation and improve the safety and protection offered by a rotavirus vaccine.

Our group hosts the World Health Organization (WHO) Collaborating Centre for Child Health, the WHO Rotavirus Regional Reference Laboratory for the Western-Pacific Region and the Australian Rotavirus Surveillance Program.

Our projects

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 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 has assisted in the development of a large scale manufacturing 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

Currently 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 as 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 at Murdoch Children's Research Institute supports Government and Reference Laboratories in the Western-Pacific region in the laboratory diagnosis of rotavirus infection.  

Specific projects include:

• The Laboratory takes part 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 takes part in the 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
• Australian Government Department of Health
• GlaxoSmithKline
• Australian National Health and Medical Research Council
• PATH USA 

Collaborations

• Bill and Melinda Gates Foundation
• World Health Organisation  
• PT Bio Farma Ltd, Indonesia
• The 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

Featured publications

• Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: A randomized, double-blind, four-arm parallel group dose-ranging study.
  Witte D, Handley A, Jere K, Bogandovic N, Mpakiza A, Turner A, Pavlic D, Bonidace K, Mandolo J, Suryawijaya Ong D, Bonnici R, Justice F, Bar-zeev N, Iturriza-Gomara M, Donato CM, Cowley D, Barnes GL, Cunliffe NA, Bines JE. Lancet Infectious Disease 2021 (in press).
  
  
• Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.
  Bines JE, At Thobari J, Satria CD, Handley A, Watts E, Cowley D, Nirwati H, Ackland J, Standish J, Justice F, Byars G, Lee KJ, Barnes GL, Bachtiar N, Viska Icanervilia A, Boniface K, Bogadanovic-Sakran N, Pavlic D, Bishop RF, Kirkwood CD, Buttery JP, Soenarto Y. New England Journal of Medicine. 2018; 378:719-30.
  
  
• Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered in a birth dose or an infant dose schedule: A randomised, double blind, placebo controlled trial.
  Bines JE, Danchin MD, Jackson P, Handley A, Watts E, Crowley D, Lee K, West A, Chen M-Y, Barnes GL, Justice F, Buttery J, Taylor B, Kirkwood C. Lancet Infectious Diseases, 2015; 15(12):1389-97. Phase IIa trial provides evidence that the RV3-BB vaccine was safe and immunogenic when given in a neonatal of infant schedule.
  
  
• Rotavirus disease and genotype diversity in older children and adults in Australia. 
  Donato CM, Roczo-Farkas S, Kirkwood CD, Barnes GL, Bines JE. The Journal of Infectious Diseases. 2020 jul 21
  
  
• The impact of rotavirus vaccines on genotype diversity: a comprehensive analysis of two decades of Australian surveillance data.
  Roczo-Farkas S, Kirkwood C, Cowley D, Barnes G, Bishop R, Bogdanovic-Sakran N, Boniface K, Donato C, Bines JE. Journal of Infectious Diseases 2018 ; 218:5 46-554