Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome

Emerging evidence demonstrates a connection between microbiome composition and suboptimal response to vaccines (vaccine hyporesponse). Harnessing the interaction between microbes and the immune system could provide novel therapeutic strategies for improving vaccine response. Currently we do not full...

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Autores principales: Gokul Swaminathan, Michael Citron, Jianying Xiao, James E. Norton, Abigail L. Reens, Begüm D. Topçuoğlu, Julia M. Maritz, Keun-Joong Lee, Daniel C. Freed, Teresa M. Weber, Cory H. White, Mahika Kadam, Erin Spofford, Erin Bryant-Hall, Gino Salituro, Sushma Kommineni, Xue Liang, Olga Danilchanka, Jane A. Fontenot, Christopher H. Woelk, Dario A. Gutierrez, Daria J. Hazuda, Geoffrey D. Hannigan
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/c57141bfb4b545c0b73222a00565d3e1
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spelling oai:doaj.org-article:c57141bfb4b545c0b73222a00565d3e12021-11-25T19:11:27ZVaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome10.3390/vaccines91113402076-393Xhttps://doaj.org/article/c57141bfb4b545c0b73222a00565d3e12021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1340https://doaj.org/toc/2076-393XEmerging evidence demonstrates a connection between microbiome composition and suboptimal response to vaccines (vaccine hyporesponse). Harnessing the interaction between microbes and the immune system could provide novel therapeutic strategies for improving vaccine response. Currently we do not fully understand the mechanisms and dynamics by which the microbiome influences vaccine response. Using both mouse and non-human primate models, we report that short-term oral treatment with a single antibiotic (vancomycin) results in the disruption of the gut microbiome and this correlates with a decrease in systemic levels of antigen-specific IgG upon subsequent parenteral vaccination. We further show that recovery of microbial diversity before vaccination prevents antibiotic-induced vaccine hyporesponse, and that the antigen specific IgG response correlates with the recovery of microbiome diversity. RNA sequencing analysis of small intestine, spleen, whole blood, and secondary lymphoid organs from antibiotic treated mice revealed a dramatic impact on the immune system, and a muted inflammatory signature is correlated with loss of bacteria from <i>Lachnospiraceae</i>, <i>Ruminococcaceae</i>, and <i>Clostridiaceae</i>. These results suggest that microbially modulated immune pathways may be leveraged to promote vaccine response and will inform future vaccine design and development strategies.Gokul SwaminathanMichael CitronJianying XiaoJames E. NortonAbigail L. ReensBegüm D. TopçuoğluJulia M. MaritzKeun-Joong LeeDaniel C. FreedTeresa M. WeberCory H. WhiteMahika KadamErin SpoffordErin Bryant-HallGino SalituroSushma KommineniXue LiangOlga DanilchankaJane A. FontenotChristopher H. WoelkDario A. GutierrezDaria J. HazudaGeoffrey D. HanniganMDPI AGarticlemicrobiomevaccinesimmunityMedicineRENVaccines, Vol 9, Iss 1340, p 1340 (2021)
institution DOAJ
collection DOAJ
language EN
topic microbiome
vaccines
immunity
Medicine
R
spellingShingle microbiome
vaccines
immunity
Medicine
R
Gokul Swaminathan
Michael Citron
Jianying Xiao
James E. Norton
Abigail L. Reens
Begüm D. Topçuoğlu
Julia M. Maritz
Keun-Joong Lee
Daniel C. Freed
Teresa M. Weber
Cory H. White
Mahika Kadam
Erin Spofford
Erin Bryant-Hall
Gino Salituro
Sushma Kommineni
Xue Liang
Olga Danilchanka
Jane A. Fontenot
Christopher H. Woelk
Dario A. Gutierrez
Daria J. Hazuda
Geoffrey D. Hannigan
Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome
description Emerging evidence demonstrates a connection between microbiome composition and suboptimal response to vaccines (vaccine hyporesponse). Harnessing the interaction between microbes and the immune system could provide novel therapeutic strategies for improving vaccine response. Currently we do not fully understand the mechanisms and dynamics by which the microbiome influences vaccine response. Using both mouse and non-human primate models, we report that short-term oral treatment with a single antibiotic (vancomycin) results in the disruption of the gut microbiome and this correlates with a decrease in systemic levels of antigen-specific IgG upon subsequent parenteral vaccination. We further show that recovery of microbial diversity before vaccination prevents antibiotic-induced vaccine hyporesponse, and that the antigen specific IgG response correlates with the recovery of microbiome diversity. RNA sequencing analysis of small intestine, spleen, whole blood, and secondary lymphoid organs from antibiotic treated mice revealed a dramatic impact on the immune system, and a muted inflammatory signature is correlated with loss of bacteria from <i>Lachnospiraceae</i>, <i>Ruminococcaceae</i>, and <i>Clostridiaceae</i>. These results suggest that microbially modulated immune pathways may be leveraged to promote vaccine response and will inform future vaccine design and development strategies.
format article
author Gokul Swaminathan
Michael Citron
Jianying Xiao
James E. Norton
Abigail L. Reens
Begüm D. Topçuoğlu
Julia M. Maritz
Keun-Joong Lee
Daniel C. Freed
Teresa M. Weber
Cory H. White
Mahika Kadam
Erin Spofford
Erin Bryant-Hall
Gino Salituro
Sushma Kommineni
Xue Liang
Olga Danilchanka
Jane A. Fontenot
Christopher H. Woelk
Dario A. Gutierrez
Daria J. Hazuda
Geoffrey D. Hannigan
author_facet Gokul Swaminathan
Michael Citron
Jianying Xiao
James E. Norton
Abigail L. Reens
Begüm D. Topçuoğlu
Julia M. Maritz
Keun-Joong Lee
Daniel C. Freed
Teresa M. Weber
Cory H. White
Mahika Kadam
Erin Spofford
Erin Bryant-Hall
Gino Salituro
Sushma Kommineni
Xue Liang
Olga Danilchanka
Jane A. Fontenot
Christopher H. Woelk
Dario A. Gutierrez
Daria J. Hazuda
Geoffrey D. Hannigan
author_sort Gokul Swaminathan
title Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome
title_short Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome
title_full Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome
title_fullStr Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome
title_full_unstemmed Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome
title_sort vaccine hyporesponse induced by individual antibiotic treatment in mice and non-human primates is diminished upon recovery of the gut microbiome
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/c57141bfb4b545c0b73222a00565d3e1
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