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

Hera Nirwati, Christina Bronowski, Eleanor A Lyons, Jarir At Thobari, Julie E Bines, Josef Wagner, Nada Bogdanovic-Sakran, Karen Boniface, Amanda Handley, Edward P K Parker, Daniel Pavlic, Yati Soenarto, Jim P Buttery, Frances Justice, Ashley Mpakiza, Emma Watts, Cahya Dewi Satria, Celeste M Donato, Desiree Witte, Naor Bar-Zeev, Khuzwayo C Jere, Nigel A Cunliffe, Miren Iturriza-Gomara, Rhian Bonnici, Darren Suryawijaya Ong, Jonathan Mandolo, Ann Turner

Journal: Nature communications 2025;16(1):3432

PMID: 40210877

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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.

Address: Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia. [email protected].; Respiratory Virus and Microbiome Initiative, Wellcome Sanger Institute, Hinxton, UK. [email protected].; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. [email protected].; Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia.; Medicines Development for Global Health, Melbourne, Victoria, Australia.; Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia.; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.; Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia.; Department of Infectious Disease Epidemiology and International Health, London School of Hygiene and Tropical Medicine, London, UK.; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.; Department of Pharmacology and Therapy, Faculty of Medicine, Nursing and Universitas Gadjah Mada, Yogyakarta, Indonesia.; Pediatric Research Office, Department of Pediatrics, Faculty of Medicine, Nursing and Universitas Gadjah Mada, Yogyakarta, Indonesia.; Pediatric Research Office, Department of Pediatrics, Faculty of Medicine, Nursing and Universitas Gadjah Mada, Yogyakarta, Indonesia.; Department of Microbiology, Faculty of Medicine, Nursing and Universitas Gadjah Mada, Yogyakarta, Indonesia, Faculty of Medicine, Nursing and Universitas Gadjah Mada, Yogyakarta, Indonesia.; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.; Malawi Liverpool Wellcome Programme, Blantyre, P.O. Box 30096, Chichiri, Malawi.; Malawi Liverpool Wellcome Programme, Blantyre, P.O. Box 30096, Chichiri, Malawi.; Malawi Liverpool Wellcome Programme, Blantyre, P.O. Box 30096, Chichiri, Malawi.; Department of Clinical Science, Liverpool School of Tropical Medicine, Liverpool, UK.; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.; GSK Vaccines for Global Health Institute, Sienna, Italy.; Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia.; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.; Department of Infectious Diseases, Royal Children's Hospital, Parkville, Australia.; Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia. [email protected].; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. [email protected].; Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Australia. [email protected].

DOI: 10.1038/s41467-025-58632-6

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MeSH Terms: Humans, Gastrointestinal Microbiome, Rotavirus Vaccines, Rotavirus Infections, Infant, Infant, Newborn, Rotavirus, Female, Immunoglobulin A, Feces, Virus Shedding, Male, Vaccines, Attenuated, Antibodies, Viral, Immunization Schedule, Malawi, Indonesia, Seroconversion, Vaccination