Australian - Indonesian researchers collaborate on development of a birth dose rotavirus vaccine which could benefit millions of children

Researchers from the Murdoch Children’s Research Institute (MCRI) have developed a rotavirus vaccine that provides earlier protection from dehydrating diarrhoea for infants and young children.  

Diarrhoea is one of the leading causes of child illness and death, and rotavirus is the most common cause of severe diarrhoea. Globally rotaviruses cause approximately 215,000 deaths in children under five years.  

Children in Indonesia continue to face the dangers of rotavirus gastroenteritis. It is estimated to cause 10,000 child deaths, over 200,000 hospitalisations and almost 600,000 clinic presentations in children under 5 in Indonesia every year. The collaborative work of Australian and Indonesian researchers is a crucial step forward to potentially saving thousands of lives.

In a world-first clinical trial conducted in Indonesia, the RV3-BB vaccine was administered to babies within their first five days of life. Current rotavirus vaccines can only be administered to children older than six weeks, which leaves newborn babies particularly vulnerable to rotavirus infection.

The trial involving 1649 babies saw severe rotavirus gastroenteritis reduced in babies receiving the vaccine in a country where rotavirus vaccines are not routinely available to children as part of the National Immunization Program.

“This study involved 25 primary health centres and hospitals from District Klaten, Central Java and District Sleman, Yogyakarta. The babies in the study were followed until 18 months of age. The study follow up was successful with very high completion rates (more than 96 per cent )” Associate Professor Jarir At Thobari said. 

The oral vaccine was given in three single doses, the first within five days of birth. A small volume of liquid placed in the baby’s mouth provided protection against severe rotavirus gastroenteritis. The results, published in the New England Journal of Medicine, have found that after three doses of RV3BB administered from birth, 94 per cent of infants were protected in their first year of life against severe rotavirus gastroenteritis. 75 per cent of infants were protected to 18 months of age.

Professor Julie Bines, the study’s lead researcher from MCRI; a professor at the  University of Melbourne; and  a prominent gastroenterologist at the Royal Children’s Hospital, further emphasised the importance of a birth dose.

“In lower resource settings, birth is often the best contact between mother, baby and health services. RV3-BB provides an ideal vaccination opportunity. This disease doesn’t discriminate – it infects children worldwide under the age of five – irrespective of what environment you live in,” Professor Bines said.  

Professor Yati Soenarto, a regional leader in paediatric gastroenterology and rotavirus research in Indonesia, had shown that rotavirus is responsible for the majority of diarrhoeal infections causing hospitalisation of infants and young children in Indonesia. 

“By starting vaccination from birth we are able to offer babies protection from rotavirus disease by three months of age, after this time, babies sometimes miss later vaccination opportunities, when their risk of the severe rotavirus disease is high” Professor Soenarto said.

“The rotavirus vaccines that are currently available work very well in places like Australia, the US and Europe but they don’t seem to work as well in low income settings in Africa and Asia where severe gastroenteritis is common and many children die,” Professor Bines said.

The World Health Organisation recommends that all children receive a rotavirus vaccine, however ~94 million infants still do not have access to the vaccine. In an effort to make rotavirus vaccine more readily accessible to infants worldwide, MCRI seek to license RV3-BB to manufacturers able to produce vaccines at large scale and at an accessible price.  MCRI have been working with the Indonesian vaccine manufacturer PT Bio Farma under license to produce the RV3-BB vaccine.

Duncan Steele, Deputy Director and Strategic Lead for Enteric Vaccines at the Bill & Melinda Gates Foundation noted that “Thanks to increased investments in global health in the last 25 years, we have seen dramatic improvements in child health but it is unconscionable that children are still dying by the hundreds of thousands every year from diseases that are preventable and curable, such as diarrhoea. We know rotavirus vaccines work to save young lives and prevent hospitalizations in every country where they are used. The successful clinical trial in Indonesia, coupled with commitment from Bio Farma PT to produce the vaccine, provides confidence in a vaccine that has the potential to have a major impact in Indonesia, and ultimately globally. Furthermore, the vision of the Australian research team in pursuing a global clinical development, including clinical trials in Australia, New Zealand, Indonesia and Africa highlights the promise of a birth dose rotavirus vaccine for all children.”      

The success of the RV3-BB vaccine represents a significant scientific and global health achievement. It is the culmination of more than four decades of work which started with Professor Ruth Bishop discovering rotavirus and leading critical work at MCRI to understand more about this important virus. The RV3-BB vaccine is based on a strain that was isolated by Professor Bishop, Professor Graeme Barnes and their colleagues in the nurseries of the Royal Women’s Hospital, which did not cause symptoms in the babies who were infected and instead provided them with protection against severe gastroenteritis. 

“In 1973, Professor Ruth Bishop led a team of researchers to make one of the most important Australian contributions to global child health,” Professor Bines said. “Our aim is to build on this legacy by developing an effective rotavirus vaccine that prevents rotavirus disease from birth for the world’s children.”

The trial was generously funded by the National Health and Medical Research Council (NHMRC), Bill & Melinda Gates Foundation and PT Bio Farma.