@article{cf4e5184d5014c76a91e5bb121e7ab11,
title = "Enteric virome negatively affects seroconversion following oral rotavirus vaccination in a longitudinally sampled cohort of Ghanaian infants",
abstract = "Rotavirus vaccines (RVVs) have substantially diminished mortality from severe rotavirus (RV) gastroenteritis but are significantly less effective in low- and middle-income countries (LMICs), limiting their life-saving potential. The etiology of RVV's diminished effectiveness remains incompletely understood, but the enteric microbiota has been implicated in modulating immunity to RVVs. Here, we analyze the enteric microbiota in a longitudinal cohort of 122 Ghanaian infants, evaluated over the course of 3 Rotarix vaccinations between 6 and 15 weeks of age, to assess whether bacterial and viral populations are distinct between non-seroconverted and seroconverted infants. We identify bacterial taxa including Streptococcus and a poorly classified taxon in Enterobacteriaceae as positively correlating with seroconversion. In contrast, both bacteriophage diversity and detection of Enterovirus B and multiple novel cosaviruses are negatively associated with RVV seroconversion. These findings suggest that virome-RVV interference is an underappreciated cause of poor vaccine performance in LMICs.",
keywords = "bacteriophage, immunization, metagenomic sequencing, microbiome, microbiota, phageome, rotavirus vaccine performance, transkingdom interaction, vaccination, viral bacterial co-infection",
author = "Kim, {Andrew HyoungJin} and George Armah and Francis Dennis and Leran Wang and Rachel Rodgers and Lindsay Droit and Baldridge, {Megan T.} and Handley, {Scott A.} and Harris, {Vanessa C.}",
note = "Funding Information: We acknowledge and thank all the infants and their families who participated in this study and the staff members of the RVV trial team in Ghana for their work in conducting this study; the staff at the Noguchi Memorial Institute for Medical Research in Accra, Ghana; Monica McNeal and her staff at the Laboratory of Specialized Clinical Studies, Cincinnati Children's Hospital, who performed all the immunoglobulin testing for the original dosing studies; Duncan Steele for his contribution to the original dosing study in Ghana; and Lauren Gazley for her contribution to the original dosing study in Ghana. We are grateful to members of the Handley and Baldridge laboratories for helpful discussions. This was work was supported by a grant from the Bill and Melinda Gates Foundation (OPP1157923). M.T.B. was supported by R01 OD024917, R01 AI139314; Children's Discovery Institute of Washington University and St. Louis Children's Hospital Interdisciplinary Research Initiative grant (MI-II-2019-790); and the Mathers Foundation. A.H.K. was supported by T32 AI007163. Conceptualization, V.C.H.; methodology, S.A.H. V.C.H. and G.A.; investigation, L.D. G.A. and F.D.; software, A.H.K. S.A.H. L.W. and R.R.; formal analysis, A.H.K. and S.A.H.; resources, G.A. F.D. S.A.H. and M.T.B.; writing ? original draft, A.H.K. and V.C.H.; writing ? review and editing, A.H.K. V.C.H. M.T.B. S.A.H. F.D. and G.A.; funding acquisition, V.C.H.; visualization, A.H.K.; supervision, M.T.B. S.A.H. and V.C.H. The authors declare no competing interests. Funding Information: We acknowledge and thank all the infants and their families who participated in this study and the staff members of the RVV trial team in Ghana for their work in conducting this study; the staff at the Noguchi Memorial Institute for Medical Research in Accra, Ghana; Monica McNeal and her staff at the Laboratory of Specialized Clinical Studies, Cincinnati Children{\textquoteright}s Hospital, who performed all the immunoglobulin testing for the original dosing studies; Duncan Steele for his contribution to the original dosing study in Ghana; and Lauren Gazley for her contribution to the original dosing study in Ghana. We are grateful to members of the Handley and Baldridge laboratories for helpful discussions. This was work was supported by a grant from the Bill and Melinda Gates Foundation ( OPP1157923 ). M.T.B. was supported by R01 OD024917 , R01 AI139314 ; Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital Interdisciplinary Research Initiative grant ( MI-II-2019-790 ); and the Mathers Foundation . A.H.K. was supported by T32 AI007163 . Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = jan,
day = "12",
doi = "https://doi.org/10.1016/j.chom.2021.12.002",
language = "English",
volume = "30",
pages = "110--123.e5",
journal = "CELL Host & Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",
}