Dose-finding trial paves way for new rotavirus vaccine to prevent a deadly diarrheal disease from birth

Rotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. The unique characteristics of RV3-BB, with the first dose given soon after birth, has the potential to make a significant impact on rotavirus diarrhea disease burden in children in Africa and Asia.

Researchers from the Murdoch Children's Research Institute (MCRI), the Malawi Liverpool Wellcome Clinical Research Programme and University of Liverpool have found a reduced dose of an Australian-developed rotavirus vaccine produced a robust immune response in children at risk from deadly diarrheal disease in Africa.

Rotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. Although 114 countries have now introduced a rotavirus vaccine, there are still over 80 million or 45% of children less than 5 years of age that do not receive a rotavirus vaccine.

Developed from a unique neonatal rotavirus strain in Melbourne, the RV3-BB vaccine is given to babies from birth with the potential to improve the level of protection, limit barriers to timely administration and improve the safety of rotavirus vaccines.

The phase 2 clinical trial, published in Lancet Infectious Diseases, was co-led by the Murdoch Institute's Professor Julie Bines and Professor Nigel Cunliffe from the University of Liverpool. It assessed the safety and immune reaction to three different amounts of the RV3-BB vaccine in 711 Malawian infants at birth or in the first weeks of life.

Three doses of the mid-level amount of vaccine produced an equivalent immune response in the babies, as measured in their blood and stool, as the highest dose schedule.

Professor Bines said, "This level of immune response was similar to our Indonesian phase 2b trial, which used the higher dose. In that trial we found 94 per cent of babies that received RV3- BB soon after birth were protected from severe rotavirus diarrhea in the first year of life.

"Our results are hugely encouraging when compared to current World Health Organization prequalified and globally available vaccines. The WHO recommends all children receive a rotavirus vaccine."

Professor Cunliffe said, "While currently used rotavirus vaccines have significantly reduced illness and death from rotavirus disease in Malawi and other African countries with high child mortality, rotavirus is still the leading cause of diarrheal deaths in these settings. Our data from Malawi offer new hope that the RV3-BB neonatal rotavirus vaccine can further reduce the high burden of disease still attributed to this diarrheal pathogen."

Head of Virology at the Malawi Liverpool Wellcome Clinical Research Programme Dr Khuzwayo Jere said, 'It is exciting that the neonatal RV3-BB vaccine was well tolerated in Malawian children in both neonatal and infant schedule when co-administered with Expanded Programme on Immunisation vaccines.

Deputy Director of Global Health at the Bill & Melinda Gates Foundation Dr Duncan Steele said, "Despite being preventable with safe and effective vaccines, rotavirus remains a leading infectious killer of young children worldwide," said Duncan Stelle, Deputy Director of the Enteric Diarrheal Diseases team at the Bill & Melinda Gates Foundation. "It is gratifying to see this neonatal rotavirus vaccine, which was initially developed by Professors Ruth Bishop and Graeme Barnes at Murdoch Children's Research Institute, perform well in an African population with high rotavirus disease burden. These results support those observed in Indonesia and New Zealand showing great promise to reduce the high burden of rotavirus that we still see in Africa and Asia. We are pleased to support the Murdoch Children's Research Institute and the University of Liverpool on this important work."

To make rotavirus vaccine more readily accessible, Murdoch Children's has made RV3-BB available to manufacturers for license to produce vaccines at large scale for an accessible price.

Current licensee, Indonesian vaccine manufacturer PT BioFarma, is conducting a phase 3 clinical trial of RV3-BB in Indonesia with results due to be announced in 2023.

In 2021, Professor Bines was awarded an Australian Museum Eureka Prize, one of the most prestigious awards given to Australian researchers, for her work in developing RV3-BB.

RV3-BB represents a significant scientific and global health achievement. It began four decades ago, when Professor Ruth Bishop discovered rotavirus and led critical work at the Murdoch Children's to understand more about this important virus.

"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."