
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.
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
• 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
• 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
- Direct and indirect effects of rotavirus vaccine on diarrhoea, five years following national introduction in Fiji 2020
- Genetic characterisation of novel G29P[14] and G10P[11] rotavirus strains from African buffalo. 2020
- Human Neonatal Rotavirus Vaccine (RV3-BB) Produces Vaccine Take Irrespective of Histo-Blood Group Antigen Status. 2020
- Luminal microbiota related to Crohn's disease recurrence after surgery. 2020
- Next-generation rotavirus vaccines: important progress but work still to be done. 2020
- Rotavirus disease and genotype diversity in older children and adults in Australia. 2020
- Rotavirus specific maternal antibodies and immune response to RV3-BB rotavirus vaccine in central java and yogyakarta, Indonesia. 2020
- Antimicrobial use in an Indonesian community cohort 0-18 months of age. 2019
- Australian Rotavirus Surveillance Program: Annual Report, 2017 2019
- Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials. 2019
- Higher Sun Exposure is Associated With Lower Risk of Pediatric Inflammatory Bowel Disease: A Matched Case-control Study. 2019
- Immunogenicity of four doses of oral poliovirus vaccine when co-administered with the human neonatal rotavirus vaccine (RV3-BB). 2019
- Monitoring of long-term parenteral nutrition in children with intestinal failure. 2019
- Norovirus and rotavirus infections in children less than five years of age hospitalized with acute gastroenteritis in Indonesia. 2019
- Phylogenetic and immunoinformatic analysis of VP4, VP7, and NSP4 genes of rotavirus strains circulating in children with acute gastroenteritis in Indonesia. 2019
- Rotavirus Epidemiology and Monovalent Rotavirus Vaccine Effectiveness in Australia: 2010-2017. 2019
- The Microbiome in Paediatric Crohn's Disease-A Longitudinal, Prospective, Single-Centre Study. 2019
- Variation of Gut Mucosal Microbiome With Anti-Saccharomyces cerevisiae Antibody Status in Pediatric Crohn Disease. 2019
- Variation of Gut Mucosal Microbiome with ASCA Status in Pediatric Crohn's Disease. 2019
- Characterization of the fecal virome in dogs with chronic enteropathy. 2018
- Gamma-irradiated rotavirus: A possible whole virus inactivated vaccine. 2018
- Molecular characterisation of rotavirus strains detected during a clinical trial of the human neonatal rotavirus vaccine (RV3-BB) in Indonesia. 2018
- Molecular characterisation of rotavirus strains detected during a clinical trial of the human neonatal rotavirus vaccine (RV3-BB) in Indonesia. 2018
- Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years. 2018
- Rotavirus vaccine: a single birth dose? 2018
- Serological responses to rotavirus NSP2 following administration of RV3-BB human neonatal rotavirus vaccine. 2018
- Single-dose rotavirus vaccine at birth: is it effective or safe? - Authors' reply. 2018
- Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All. 2018
- Australian Rotavirus Surveillance Program: Annual Report, 2016. 2017
- Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics. 2017
- Detection of viruses in weekly stool specimens collected during the first 2 years of life: A pilot study of five healthy Australian infants in the rotavirus vaccine era. 2017
- Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction. 2017
- Microbial Factors Associated with Postoperative Crohn's Disease Recurrence. 2017
- Nutritional status, exclusive breastfeeding and management of acute respiratory illness and diarrhea in the first 6 months of life in infants from two regions of Indonesia. 2017
- Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine. 2017
- Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand. 2017
- The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation. 2017
- Australian Rotavirus Surveillance Program annual report, 2015. 2016
- CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies. 2016
- Emergence of a novel equine-like G3P[8] inter-genogroup reassortant rotavirus strain associated with gastroenteritis in Australian children. 2016
- Increased Rotavirus Prevalence in Diarrheal Outbreak Precipitated by Localized Flooding, Solomon Islands, 2014. 2016
- Options for improving effectiveness of rotavirus vaccines in developing countries. 2016
- A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam. 2015
- Are identity badges and lanyards in pediatrics potentially contaminated with viral pathogens? 2015
- Association between specific mucosa-associated microbiota in Crohn's disease at the time of resection and subsequent disease recurrence: a pilot study. 2015
- Australian Rotavirus Surveillance Program annual report, 2014. 2015
- Comparison of test specificities of commercial antigen-based assays and in-house PCR methods for detection of rotavirus in stool specimens. 2015
- Conquering rotavirus: from discovery to global vaccine implementation. 2015
- Emerging OP354-Like P[8] Rotaviruses Have Rapidly Dispersed from Asia to Other Continents. 2015
- Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction. 2015
- HIV-1 transcriptional regulation in the central nervous system and implications for HIV cure research. 2015
- Morbidity and mortality in hospitalised neonates in central Vietnam. 2015
- Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review. 2015
- Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial. 2015
- Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial. 2015
- Characterization of a G1P[8] rotavirus causing an outbreak of gastroenteritis in the Northern Territory, Australia, in the vaccine era. 2014
- Characterization of G2P[4] rotavirus strains associated with increased detection in Australian states using the RotaTeq® vaccine during the 2010-2011 surveillance period. 2014
- Characterization of G2P[4] rotavirus strains causing outbreaks of gastroenteritis in the Northern Territory, Australia, in 1999, 2004 and 2009. 2014
- Genetic characterization of a novel G3P[14] rotavirus strain causing gastroenteritis in 12 year old Australian child. 2014
- Geographic variation in the eukaryotic virome of human diarrhea. 2014
- Intussusception and rotavirus vaccines: consensus on benefits outweighing recognized risk. 2014
- Intussusception is associated with the detection of adenovirus C, enterovirus B and rotavirus in a rotavirus vaccinated population. 2014
- Novel porcine-like human G26P[19] rotavirus identified in hospitalized paediatric diarrhoea patients in Ho Chi Minh City, Vietnam. 2014
- Outcomes of childhood asthma to the age of 50 years. 2014
- Rotavirus infection induces transient pancreatic involution and hyperglycemia in weanling mice. 2014
- SNP genotyping of animal and human derived isolates of Mycobacterium avium subsp. paratuberculosis. 2014
- The association between childhood asthma and adult chronic obstructive pulmonary disease. 2014
- Trends in eczema, rhinitis, and rye grass sensitization in a longitudinal asthma cohort. 2014
- What can rotavirus vaccines teach us about rotavirus? 2014
- Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing. 2013
- Changes in the epidemiology of gastroenteritis in a paediatric short stay unit following the introduction of rotavirus immunisation. 2013
- Crohn’s disease: towards improving postsurgical outcomes. 2013
- Enteral nutrition in Crohn's disease: an underused therapy 2013
- Identification and characterization of antibody-binding epitopes on the norovirus GII.3 capsid. 2013
- Impact of ethnicity, geography, and disease on the microbiota in health and inflammatory bowel disease. 2013
- Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine. 2013
- Pseudomonas infection in children with early-onset Crohn's disease: an association with a mutation close to PSMG1. 2013
- The importance of intergenic recombination in norovirus GII.3 evolution. 2013
- TLR4, IL10RA, and NOD2 mutation in paediatric Crohn's disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression. 2013
- Yellow is pale: The complications and challenges of late diagnosis of extrahepatic biliary atresia 2013
- Bacterial Dysbiosis Associated With Crohn’s Disease: Advances in Gut Metagenomic Analysis 2012
- Characterisation of a G9P[8] rotavirus strain identified during a gastroenteritis outbreak in Alice Springs, Australia post Rotarix (TM) vaccine introduction 2012
- Characterisation of a G9P[8] rotavirus strain identified during a gastroenteritis outbreak in Alice Springs, Australia post Rotarix™ vaccine introduction. 2012
- Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. 2012
- Current knowledge and systematic review of viruses associated with Crohn's disease. 2012
- Group A rotavirus universal mass vaccination: how and to what extent will selective pressure influence prevalence of rotavirus genotypes? 2012
- Identification of Strains of RotaTeq Rotavirus Vaccine in Infants With Gastroenteritis Following Routine Vaccination 2012
- Rotavirus cerebellitis: new aspects to an old foe? 2012
- Rotavirus genotypes in Malaysia and Universal rotavirus vaccination 2012
- Rotavirus genotypes in Malaysia and universal rotavirus vaccination. 2012
- Selection and evolutionary analysis in the nonstructural protein NSP2 of rotavirus A 2012
- Surveillance and molecular characterization of group a rotaviruses in goroka, Papua New Guinea 2012
- Case-control evaluation of the effectiveness of the G1P[8] human rotavirus vaccine during an outbreak of rotavirus G2P[4] infection in central Australia. 2011
- Characterization of norovirus strains in Australian children from 2006 to 2008: Prevalence of recombinant strains. 2011
- Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period 2011
- Distribution of Rotavirus Genotypes After Introduction of Rotavirus Vaccines, Rotarix (R) and RotaTeq (R), into the National Immunization Program of Australia 2011
- Exploring the Zoonotic Potential of Mycobacterium avium Subspecies paratuberculosis through Comparative Genomics 2011
- Expression profile of genes involved in pathogenesis of paediatric Crohn's disease. 2011
- Identification of an Antibody Binding Epitope on the Rotavirus Non-Structural Protein NSP2 Using Phage Display Analysis. 2011
- Maternal antibodies to rotavirus: could they interfere with live rotavirus vaccines in developing countries? 2011
- Mycobacterium avium Subspecies paratuberculosis in Children with Early-onset Crohn's Disease: A Longitudinal Follow-up Study 2011
- Optimizing immunization in pediatric special risk groups. 2011
- Phylogenetic analysis of rotavirus A NSP2 gene sequences and evidence of intragenic recombination. 2011
- Rare Rotavirus Strains in Children with Severe Diarrhea, Malaysia 2011
- Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule 2011
- Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG) 2011
- Risk factors for intussusception in infants in Vietnam and Australia: adenovirus implicated, but not rotavirus. 2006
- Acute intussusception in infants and children as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. 2004