TY - JOUR
T1 - Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity
T2 - A Human, Randomized-Control Proof-of-Concept Trial
AU - Harris, Vanessa C.
AU - Haak, Bastiaan W.
AU - Handley, Scott A.
AU - Jiang, Baoming
AU - Velasquez, Daniel E.
AU - Hykes, Barry L.
AU - Droit, Lindsay
AU - Berbers, Guy A.M.
AU - Kemper, Elles Marleen
AU - van Leeuwen, Ester M.M.
AU - Boele van Hensbroek, Michael
AU - Wiersinga, Willem Joost
N1 - Funding Information:
This research was funded by a research grant from the Emma Children's Hospital Foundation, Academic Medical Center, Amsterdam (Stichting Emma Foundation) (project number WAR004-2015-03-001 to M.B.H. and V.CH.). The study authors would like to thank the participants in this study for their willingness to enroll in this study, their commitment, their time, and their enthusiasm. We would also like to thank Rosan vd Lee at the Center for Molecular Medicine in the AMC for their laboratory time and excellent technical assistance. We would like to thank Sung-Sil Moon, Yuhuan Wang, and Dr. Umesh Parashar at the Division of Viral Diseases Centers for Disease Control and Prevention and Professor Carlo Giaquinto at the Department of Pediatrics at the University of Padova for their support, advice, and insight. We would also like to thank Herbert “Skip” W. Virgin for his support of the microbiome library preparation within his laboratory facility. Finally, this study would not have been possible without the enthusiasm and commitment of Professor Joseph (Joep) Lange, who died prior to its publication.
Funding Information:
This research was funded by a research grant from the Emma Children’s Hospital Foundation , Academic Medical Center, Amsterdam (Stichting Emma Foundation) (project number WAR004-2015-03-001 to M.B.H. and V.CH.). The study authors would like to thank the participants in this study for their willingness to enroll in this study, their commitment, their time, and their enthusiasm. We would also like to thank Rosan vd Lee at the Center for Molecular Medicine in the AMC for their laboratory time and excellent technical assistance. We would like to thank Sung-Sil Moon, Yuhuan Wang, and Dr. Umesh Parashar at the Division of Viral Diseases Centers for Disease Control and Prevention and Professor Carlo Giaquinto at the Department of Pediatrics at the University of Padova for their support, advice, and insight. We would also like to thank Herbert “Skip” W. Virgin for his support of the microbiome library preparation within his laboratory facility. Finally, this study would not have been possible without the enthusiasm and commitment of Professor Joseph (Joep) Lange, who died prior to its publication.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/8/8
Y1 - 2018/8/8
N2 - Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV immunogenicity was boosted at 7 days in the narrow-spectrum group. Further, antibiotics increased fecal shedding of RV while also rapidly altering gut bacterial beta diversity. Beta diversity associated with RVV immunogenicity boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and RV shedders were identified. Despite the negative primary endpoint, this study demonstrates that microbiota modification alters the immune response to RVV and supports further exploration of microbiome manipulation to improve RVV immunogenicity. Rotavirus vaccines (RVV) are less effective in poor-resourced settings. This randomized-controlled trial in adults tested the effect of microbiome modulation via broad-spectrum, narrow-spectrum, or no antibiotics on RVV performance. Absolute anti-RV IgA titer did not change. However, antibiotics resulted in higher day-7 boosting and increased RV-antigen shedding.
AB - Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV immunogenicity was boosted at 7 days in the narrow-spectrum group. Further, antibiotics increased fecal shedding of RV while also rapidly altering gut bacterial beta diversity. Beta diversity associated with RVV immunogenicity boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and RV shedders were identified. Despite the negative primary endpoint, this study demonstrates that microbiota modification alters the immune response to RVV and supports further exploration of microbiome manipulation to improve RVV immunogenicity. Rotavirus vaccines (RVV) are less effective in poor-resourced settings. This randomized-controlled trial in adults tested the effect of microbiome modulation via broad-spectrum, narrow-spectrum, or no antibiotics on RVV performance. Absolute anti-RV IgA titer did not change. However, antibiotics resulted in higher day-7 boosting and increased RV-antigen shedding.
KW - Bacteroidetes
KW - Firmicutes
KW - Proteobacteria
KW - anti-IgA
KW - ciprofloxacin
KW - gastroenteritis
KW - gastrointestinal microbiome
KW - immunoglobulin A
KW - metronidazole
KW - microbiota
KW - oral vaccines
KW - rotavirus
KW - rotavirus infections
KW - rotavirus vaccines
KW - vaccines
KW - vancomycin
UR - https://www.scopus.com/pages/publications/85050666558
U2 - 10.1016/j.chom.2018.07.005
DO - 10.1016/j.chom.2018.07.005
M3 - Article
C2 - 30092197
AN - SCOPUS:85050666558
SN - 1931-3128
VL - 24
SP - 197-207.e4
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -