MedicalResearch.com Interview with:
Professor Julie Bines
Inaugural Victor and Loti Smorgon Professor of Paediatrics and Deputy Head of Department of Paediatrics University of Melbourne.
Murdoch Childrens Research Institute
MedicalResearch.com: What is the background for this study? Would you briefly explain the significance of Rotavirus infections?
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. This disease doesn’t discriminate – it infects children worldwide under the age of five – irrespective of what environment you live in.
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.
In a world-first clinical trial conducted in Indonesia, the oral 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. In lower resource settings, birth is often the best contact between mother, baby and health services.
The oral RV3-BB vaccine was developed from the human neonatal rotavirus strain RV3 identified in the stool of healthy newborn babies. It does not naturally cause diarrhoea like other rotaviruses. The RV3-BB vaccine program aims to take advantage of the characteristics of this novel strain to target a birth dose vaccination strategy.
MedicalResearch.com: What are the main findings?
Response: The trial involving 1649 babies saw severe rotavirus gastroenteritis reduced in babies receiving the vaccine in Indonesia, where rotavirus vaccines are not routinely available to children as part of the National Immunization Program.
When administered to newborns (with the first dose within the first few days of life), three doses of RV3-BB was associated with an efficacy of 94% against severe rotavirus gastroenteritis to 12 months of age. This means that severe rotavirus gastroenteritis was reduced by 94% in the vaccinated group (compared to babies that did not receive vaccine) to 12 months of age. Up to 18 months of age there was a 75% reduction in disease in vaccinated babies compared to those not vaccinated with RV3-BB.
One group received the RV3-BB vaccine as infants with the first dose at 8 weeks of age, matching the normal timing for rotavirus vaccination. In this group, the infant group, efficacy against severe rotavirus gastroenteritis to 12 months of age was 77% and 51% to 18 months of age, compared to babies not vaccinated.
Blood samples were collected from some participants to measure the response of the immune system to the RV3-BB vaccine. This measurement includes an assessment of serum immune response and excretion of vaccine virus in the stool. Following three doses of the RV3-BB vaccine, a vaccine response was detected in 78 of the 83 (94%) newborn vaccine group participants and 83 of the 84 (99%) infant vaccine group participants. Each group was significantly different from the placebo group.
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 RV3-BB 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.
MedicalResearch.com: What should readers take away from your report?
Response: The results for the RV3-BB vaccine compare favourably with licensed vaccines studied in similar high disease burden, low- and low-middle income countries. It is hoped that the RV3-BB vaccine will be effective from birth, offering earlier protection against rotavirus infection.
The World Health Organisation recommends that all children receive a rotavirus vaccine, however approximately 90 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.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The results of this study provide clues that may explain why the current licensed rotavirus vaccines that work well in developed countries do not seem to work as well in low-income countries in Africa and Asia. The results of this study suggest that the RV3-BB vaccine when administered to newborns results in a high level of protection from severe rotavirus disease. Whether this is due to the intrinsic characteristics of this human neonatal rotavirus strain or the factors related to the impact of this novel vaccine strain on the developing gut or immune responses in the newborn is not well understood. The intrinsic characteristics of the RV3-BB vaccine also present the potential for an increased level of protection in countries of Africa and Asia where genetic factors may place infants at risk of specific rotavirus strains. Future studies in Africa are needed to explore this possibility.
Disclosures: The trial was generously funded by the National Health and Medical Research Council (NHMRC), Bill & Melinda Gates Foundation and PT Bio Farma.
Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth
Julie E. Bines, M.D., Jarir At Thobari, Ph.D., Cahya Dewi Satria, M.D., Amanda Handley, M.P.H., Emma Watts, B.Sci., Daniel Cowley, Ph.D., Hera Nirwati, M.D., Ph.D., James Ackland, B.Sci., Jane Standish, M.B., B.S., Frances Justice, B.Sci., Gabrielle Byars, M.Bio.Med.Sci., Katherine J. Lee, Ph.D., Graeme L. Barnes, M.D., Novilia S. Bachtiar, Dr.M.Kes., Ajeng Viska Icanervilia, M.D., Karen Boniface, B.Sci., Nada Bogdanovic-Sakran, B.Sci., Daniel Pavlic, B.Sci., Ruth F. Bishop, A.O., D.Sc., Carl D. Kirkwood, Ph.D., et al
February 22, 2018 N Engl J Med 2018; 378:719-730
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