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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MDPI AG
2021
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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) |
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microbiome vaccines immunity Medicine R |
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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 |
work_keys_str_mv |
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