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

Date:
February 4, 2022
Source:
Murdoch Childrens Research Institute
Summary:
Researchers 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.



FULL STORY ==========================================================================
A phase 2 clinical trial has found that the Australian-developed neonatal rotavirus vaccine RV3-BB was safe and produced a robust immune response
in African babies. The immune response generated was similar in the
group given a reduced dose of the vaccine compared to the high dose,
providing an opportunity to reduce vaccine manufacturing costs.


========================================================================== 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." ========================================================================== Story Source: Materials provided by
Murdoch_Childrens_Research_Institute. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Desiree Witte, Amanda Handley, Khuzwayo C Jere, Nada
Bogandovic-Sakran,
Ashley Mpakiza, Ann Turner, Daniel Pavlic, Karen Boniface, Jonathan
Mandolo, Darren Suryawijaya Ong, Rhian Bonnici, Frances Justice,
Naor Bar-Zeev, Miren Iturriza-Gomara, Jim Ackland, Celeste M
Donato, Daniel Cowley, Graeme Barnes, Nigel A Cunliffe, Julie
E Bines. Neonatal rotavirus vaccine (RV3-BB) immunogenicity
and safety in a neonatal and infant administration schedule
in Malawi: a randomised, double-blind, four-arm parallel group
dose-ranging study. The Lancet Infectious Diseases, 2022; DOI:
10.1016/S1473-3099(21)00473-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220204093118.htm

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