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dc.contributor.author
Periaswamy, Balamurugan
dc.contributor.author
Maier, Lisa
dc.contributor.author
Vishwakarma, Vikalp
dc.contributor.author
Slack, Emma
dc.contributor.author
Kremer, Marcus
dc.contributor.author
Andrews-Polymenis, Helene L.
dc.contributor.author
McClelland, Michael
dc.contributor.author
Grant, Andrew J.
dc.contributor.author
Suar, Mrutyunjay
dc.contributor.author
Hardt, Wolf-Dietrich
dc.date.accessioned
2018-09-20T08:56:58Z
dc.date.available
2017-06-10T10:10:23Z
dc.date.available
2018-09-20T08:56:58Z
dc.date.issued
2012-09-24
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0045433
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/57318
dc.identifier.doi
10.3929/ethz-b-000057318
dc.description.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PLOS
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
7
en_US
ethz.journal.issue
9
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e45433
en_US
ethz.size
9 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
San Francisco, CA
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
ethz.date.deposited
2017-06-10T10:10:43Z
ethz.source
ECIT
ethz.identifier.importid
imp59364fe50119538601
ethz.ecitpid
pub:91832
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T11:41:16Z
ethz.rosetta.lastUpdated
2024-02-02T06:09:26Z
ethz.rosetta.versionExported
true
ethz.COinS
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