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

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[...

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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
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Summary: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.
ISSN:2041-1723

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