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

Autor:	Swaminathan G; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Citron M; Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, PA 19486, USA., Xiao J; Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, PA 19486, USA., Norton JE Jr; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Reens AL; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Topçuoğlu BD; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Maritz JM; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Lee KJ; Pharmacokinetics, Pharmacodynamics & Drug Metabolism, MRL, Merck & Co. Inc., Rahway, NJ 07065, USA., Freed DC; Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, PA 19486, USA., Weber TM; Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, PA 19486, USA., White CH; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Kadam M; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Spofford E; Safety Assessment and Laboratory Animal Research, MRL, Merck & Co. Inc., Boston, MA 02115, USA., Bryant-Hall E; Safety Assessment and Laboratory Animal Research, MRL, Merck & Co. Inc., Boston, MA 02115, USA., Salituro G; Pharmacokinetics, Pharmacodynamics & Drug Metabolism, MRL, Merck & Co. Inc., Rahway, NJ 07065, USA., Kommineni S; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Liang X; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Danilchanka O; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Fontenot JA; New Iberia Research Center, University of Louisiana at Lafayette, Lafayette, LA 70503, USA., Woelk CH; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Gutierrez DA; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA., Hazuda DJ; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA.; Infectious Diseases and Vaccine Research, MRL, Merck & Co., Inc., West Point, PA 19486, USA., Hannigan GD; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA.
Jazyk:	angličtina
Zdroj:	Vaccines [Vaccines (Basel)] 2021 Nov 17; Vol. 9 (11). Date of Electronic Publication: 2021 Nov 17.
DOI:	10.3390/vaccines9111340
Abstrakt:	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 Lachnospiraceae , Ruminococcaceae , and Clostridiaceae . These results suggest that microbially modulated immune pathways may be leveraged to promote vaccine response and will inform future vaccine design and development strategies.
Databáze:	MEDLINE
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