Abstract
Little is known about the role of gut microbiota in response to live oral vaccines against enteric pathogens. We examined the effect of immunization with an oral live-attenuated Shigella dysenteriae 1 vaccine and challenge with wild-type S. dysenteriae 1 on the fecal microbiota of cynomolgus macaques using 16 S rRNA analysis of fecal samples. Multi-dimensional cluster analysis identified different bacterial community types within macaques from geographically distinct locations. The fecal microbiota of Mauritian macaques, observed to be genetically distinct, harbored a high-diversity community and responded differently to Shigella immunization, as well as challenge compared to the microbiota in non-Mauritian macaques. While both macaque populations exhibited anti-Shigella antibody responses, clinical shigellosis was observed only among non-Mauritian macaques. These studies highlight the importance of further investigation into the possible protective role of the microbiota against enteric pathogens and consideration of host genetic backgrounds in conducting vaccine studies.
Highlights
Shigella species represent a group of mucosally invasive bacteria that cause bacillary dysentery, or shigellosis, in humans and nonhuman primates (NHPs) [1]
Both groups were subsequently challenged with S. dysenteriae 1 wild-type bacteria strain 1617 (1011 colony forming units (CFU) via the orogastric route) and monitored on a daily basis for development of clinical signs of disease
In this study we used 16 S rRNA pyrosequencing to define community types that characterize the fecal microbiota of cynomolgus macaques and characterized community dynamics in response to immunization and wild-type challenge
Summary
Shigella species represent a group of mucosally invasive bacteria that cause bacillary dysentery, or shigellosis, in humans and nonhuman primates (NHPs) [1]. A large inoculum (,1010 CFU) is necessary to cause bacillary dysentery in non-human primates as compared to humans Multiple factors such as diet, nutrition, and host genetics may impact vaccine efficacy [11]. This study investigates the interaction between the intestinal microbiota and live-attenuated or wild-type strains of S. dysenteriae 1 in cynomolgus macaques. We characterized the fecal microbiota in cynomolgus macaques of different geographic origins, and examined the effects of live-attenuated S. dysenteriae 1 vaccine strains on the composition of the gut microbiota. We examined correlations between distinct microbial community profiles and clinical symptoms of infection following challenge with wild-type S. dysenteriae 1 These studies represent a detailed examination of microbiota and vaccine interactions in an NHP model
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