Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB

Abstract Rotavirus vaccines are less effective in high mortality regions. A rotavirus vaccine administered at birth may overcome challenges to vaccine uptake posed by a complex gut microbiome. We investigated the association between the microbiome and vaccine responses following RV3-BB vaccine (G3P[...

Full description

Saved in:
Bibliographic Details
Main Authors: Josef Wagner, Amanda Handley, Celeste M. Donato, Eleanor A. Lyons, Daniel Pavlic, Darren Suryawijaya Ong, Rhian Bonnici, Nada Bogdanovic-Sakran, Edward P. K. Parker, Christina Bronowski, Jarir At Thobari, Cahya Dewi Satria, Hera Nirwati, Desiree Witte, Khuzwayo C. Jere, Ashley Mpakiza, Emma Watts, Ann Turner, Karen Boniface, Jonathan Mandolo, Frances Justice, Naor Bar-Zeev, Miren Iturriza-Gomara, Jim P. Buttery, Nigel A. Cunliffe, Yati Soenarto, Julie E. Bines
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58632-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849737608464171008
author Josef Wagner
Amanda Handley
Celeste M. Donato
Eleanor A. Lyons
Daniel Pavlic
Darren Suryawijaya Ong
Rhian Bonnici
Nada Bogdanovic-Sakran
Edward P. K. Parker
Christina Bronowski
Jarir At Thobari
Cahya Dewi Satria
Hera Nirwati
Desiree Witte
Khuzwayo C. Jere
Ashley Mpakiza
Emma Watts
Ann Turner
Karen Boniface
Jonathan Mandolo
Frances Justice
Naor Bar-Zeev
Miren Iturriza-Gomara
Jim P. Buttery
Nigel A. Cunliffe
Yati Soenarto
Julie E. Bines
author_facet Josef Wagner
Amanda Handley
Celeste M. Donato
Eleanor A. Lyons
Daniel Pavlic
Darren Suryawijaya Ong
Rhian Bonnici
Nada Bogdanovic-Sakran
Edward P. K. Parker
Christina Bronowski
Jarir At Thobari
Cahya Dewi Satria
Hera Nirwati
Desiree Witte
Khuzwayo C. Jere
Ashley Mpakiza
Emma Watts
Ann Turner
Karen Boniface
Jonathan Mandolo
Frances Justice
Naor Bar-Zeev
Miren Iturriza-Gomara
Jim P. Buttery
Nigel A. Cunliffe
Yati Soenarto
Julie E. Bines
author_sort Josef Wagner
collection DOAJ
description Abstract Rotavirus vaccines are less effective in high mortality regions. A rotavirus vaccine administered at birth may overcome challenges to vaccine uptake posed by a complex gut microbiome. We investigated the association between the microbiome and vaccine responses following RV3-BB vaccine (G3P[6]) administered in a neonatal schedule (dose 1: 0-5 days), or infant schedule (dose 1: 6-8 weeks) in Indonesia (Phase 2b efficacy study) (n = 478 samples/193 infants) (ACTRN12612001282875) and in Malawi (Immunigenicity study) (n = 355 samples/186 infants) (NCT03483116). Vaccine responses assessed using anti-rotavirus IgA seroconversion (IgA), stool shedding of vaccine virus and vaccine take (IgA seroconversion and/or shedding). Here we report, high alpha diversity, beta diversity differences and high abundance of Bacteroides is associated with positive vaccine take and shedding following RV3-BB administered in the neonatal schedule, but not with IgA seroconversion, or in the infant schedule. Higher alpha diversity was associated with shedding after three doses of RV3-BB in the neonatal schedule compared to non-shedders, or the placebo group. High abundance of Streptococcus and Staphylococcus is associated with no shedding in the neonatal schedule group. RV3-BB vaccine administered in a neonatal schedule modulates the early microbiome environment and presents a window of opportunity to optimise protection from rotavirus disease.
format Article
id doaj-art-e3fed057b7c6494d9a8900fa472351e2
institution DOAJ
issn 2041-1723
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-e3fed057b7c6494d9a8900fa472351e22025-08-20T03:06:52ZengNature PortfolioNature Communications2041-17232025-04-0116112110.1038/s41467-025-58632-6Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BBJosef Wagner0Amanda Handley1Celeste M. Donato2Eleanor A. Lyons3Daniel Pavlic4Darren Suryawijaya Ong5Rhian Bonnici6Nada Bogdanovic-Sakran7Edward P. K. Parker8Christina Bronowski9Jarir At Thobari10Cahya Dewi Satria11Hera Nirwati12Desiree Witte13Khuzwayo C. Jere14Ashley Mpakiza15Emma Watts16Ann Turner17Karen Boniface18Jonathan Mandolo19Frances Justice20Naor Bar-Zeev21Miren Iturriza-Gomara22Jim P. Buttery23Nigel A. Cunliffe24Yati Soenarto25Julie E. Bines26Enteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteEnteric Diseases, Murdoch Children’s Research InstituteDepartment of Infectious Disease Epidemiology and International Health, London School of Hygiene and Tropical MedicineInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolDepartment of Pharmacology and Therapy, Faculty of Medicine, Nursing and Universitas Gadjah MadaPediatric Research Office, Department of Pediatrics, Faculty of Medicine, Nursing and Universitas Gadjah MadaDepartment of Microbiology, Faculty of Medicine, Nursing and Universitas Gadjah Mada, Yogyakarta, Indonesia, Faculty of Medicine, Nursing and Universitas Gadjah MadaInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolMalawi Liverpool Wellcome Programme, BlantyreEnteric Diseases, Murdoch Children’s Research InstituteMalawi Liverpool Wellcome Programme, BlantyreEnteric Diseases, Murdoch Children’s Research InstituteMalawi Liverpool Wellcome Programme, BlantyreEnteric Diseases, Murdoch Children’s Research InstituteInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolEnteric Diseases, Murdoch Children’s Research InstituteInstitute of Infection, Veterinary and Ecological Sciences, University of LiverpoolPediatric Research Office, Department of Pediatrics, Faculty of Medicine, Nursing and Universitas Gadjah MadaEnteric Diseases, Murdoch Children’s Research InstituteAbstract Rotavirus vaccines are less effective in high mortality regions. A rotavirus vaccine administered at birth may overcome challenges to vaccine uptake posed by a complex gut microbiome. We investigated the association between the microbiome and vaccine responses following RV3-BB vaccine (G3P[6]) administered in a neonatal schedule (dose 1: 0-5 days), or infant schedule (dose 1: 6-8 weeks) in Indonesia (Phase 2b efficacy study) (n = 478 samples/193 infants) (ACTRN12612001282875) and in Malawi (Immunigenicity study) (n = 355 samples/186 infants) (NCT03483116). Vaccine responses assessed using anti-rotavirus IgA seroconversion (IgA), stool shedding of vaccine virus and vaccine take (IgA seroconversion and/or shedding). Here we report, high alpha diversity, beta diversity differences and high abundance of Bacteroides is associated with positive vaccine take and shedding following RV3-BB administered in the neonatal schedule, but not with IgA seroconversion, or in the infant schedule. Higher alpha diversity was associated with shedding after three doses of RV3-BB in the neonatal schedule compared to non-shedders, or the placebo group. High abundance of Streptococcus and Staphylococcus is associated with no shedding in the neonatal schedule group. RV3-BB vaccine administered in a neonatal schedule modulates the early microbiome environment and presents a window of opportunity to optimise protection from rotavirus disease.https://doi.org/10.1038/s41467-025-58632-6
spellingShingle Josef Wagner
Amanda Handley
Celeste M. Donato
Eleanor A. Lyons
Daniel Pavlic
Darren Suryawijaya Ong
Rhian Bonnici
Nada Bogdanovic-Sakran
Edward P. K. Parker
Christina Bronowski
Jarir At Thobari
Cahya Dewi Satria
Hera Nirwati
Desiree Witte
Khuzwayo C. Jere
Ashley Mpakiza
Emma Watts
Ann Turner
Karen Boniface
Jonathan Mandolo
Frances Justice
Naor Bar-Zeev
Miren Iturriza-Gomara
Jim P. Buttery
Nigel A. Cunliffe
Yati Soenarto
Julie E. Bines
Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB
Nature Communications
title Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB
title_full Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB
title_fullStr Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB
title_full_unstemmed Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB
title_short Early-life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine RV3-BB
title_sort early life gut microbiome associates with positive vaccine take and shedding in neonatal schedule of the human neonatal rotavirus vaccine rv3 bb
url https://doi.org/10.1038/s41467-025-58632-6
work_keys_str_mv AT josefwagner earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT amandahandley earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT celestemdonato earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT eleanoralyons earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT danielpavlic earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT darrensuryawijayaong earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT rhianbonnici earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT nadabogdanovicsakran earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT edwardpkparker earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT christinabronowski earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT jariratthobari earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT cahyadewisatria earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT heranirwati earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT desireewitte earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT khuzwayocjere earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT ashleympakiza earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT emmawatts earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT annturner earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT karenboniface earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT jonathanmandolo earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT francesjustice earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT naorbarzeev earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT mireniturrizagomara earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT jimpbuttery earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT nigelacunliffe earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT yatisoenarto earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb
AT julieebines earlylifegutmicrobiomeassociateswithpositivevaccinetakeandsheddinginneonatalscheduleofthehumanneonatalrotavirusvaccinerv3bb