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Title: Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice
Authors: Periaswamy B. 
Maier L.
Vishwakarma V.
Slack E.
Kremer M.
Andrews-Polymenis H.L.
McClelland M.
Grant A.J.
Suar M.
Hardt W.-D.
Keywords: ampicillin
immunoglobulin A
inducible nitric oxide synthase
live vaccine
reduced nicotinamide adenine dinucleotide phosphate oxidase
salmonella typhimurium vaccine
unclassified drug
animal experiment
animal model
animal tissue
antibody titer
antigen specificity
bacterial colonization
bacterial strain
colony forming unit
controlled study
drug efficacy
drug potency
drug safety
immune deficiency
immunoglobulin blood level
nucleotide sequence
Salmonella typhimurium
Membrane Glycoproteins
Mice, Knockout
NADPH Oxidase
Nitric Oxide Synthase Type II
Receptors, Tumor Necrosis Factor, Type I
Salmonella Infections, Animal
Salmonella typhimurium
Salmonella Vaccines
Vaccines, Attenuated
Salmonella typhimurium
Issue Date: 2012
Citation: Periaswamy B., Maier L., Vishwakarma V., Slack E., Kremer M., Andrews-Polymenis H.L., McClelland M., Grant A.J., Suar M., Hardt W.-D. (2012). Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice. PLoS ONE 7 (9) : e45433. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb -/- nos2 -/- animals lacking NADPH oxidase and inducible NO synthase. In cybb -/- nos2 -/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb -/- nos2 -/- mice and ?100 fold attenuated in tnfr1 -/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0045433
Rights: Attribution 4.0 International
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