TY - JOUR
T1 - The fecal microbiome and rotavirus vaccine immunogenicity in rural Zimbabwean infants
AU - the SHINE Trial Team
AU - Robertson, Ruairi C.
AU - Church, James A.
AU - Edens, Thaddeus J.
AU - Mutasa, Kuda
AU - Min Geum, Hyun
AU - Baharmand, Iman
AU - Gill, Sandeep K.
AU - Ntozini, Robert
AU - Chasekwa, Bernard
AU - Carr, Lynnea
AU - Majo, Florence D.
AU - Kirkpatrick, Beth D.
AU - Lee, Benjamin
AU - Moulton, Lawrence H.
AU - Humphrey, Jean H.
AU - Prendergast, Andrew J.
AU - Manges, Amee R.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/9/7
Y1 - 2021/9/7
N2 - Background: Oral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy. Methods: We performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity. Results: Among 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35–68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum. The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables. Conclusions: RVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries.
AB - Background: Oral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy. Methods: We performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity. Results: Among 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35–68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum. The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables. Conclusions: RVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries.
KW - Microbiome
KW - Microbiota
KW - Oral rotavirus vaccine
KW - Rotavirus
KW - Shotgun metagenomics
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U2 - 10.1016/j.vaccine.2021.07.076
DO - 10.1016/j.vaccine.2021.07.076
M3 - Article
C2 - 34393020
AN - SCOPUS:85112709201
SN - 0264-410X
VL - 39
SP - 5391
EP - 5400
JO - Vaccine
JF - Vaccine
IS - 38
ER -