Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.

2.50
Hdl Handle:
http://hdl.handle.net/10033/603509
Title:
Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.
Authors:
Kremer, Melanie; Suezer, Yasemin; Volz, Asisa; Frenz, Theresa; Majzoub, Monir; Hanschmann, Kay-Martin; Lehmann, Michael H; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Sutter, Gerd
Abstract:
Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.
Affiliation:
TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research, Braunschweig, and Hannover Medical School, Hannover, Germany.
Citation:
Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox. 2012, 8 (3):e1002557 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
2012
URI:
http://hdl.handle.net/10033/603509
DOI:
10.1371/journal.ppat.1002557
PubMed ID:
22396645
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKremer, Melanieen
dc.contributor.authorSuezer, Yaseminen
dc.contributor.authorVolz, Asisaen
dc.contributor.authorFrenz, Theresaen
dc.contributor.authorMajzoub, Moniren
dc.contributor.authorHanschmann, Kay-Martinen
dc.contributor.authorLehmann, Michael Hen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorSutter, Gerden
dc.date.accessioned2016-03-22T15:51:49Zen
dc.date.available2016-03-22T15:51:49Zen
dc.date.issued2012en
dc.identifier.citationCritical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox. 2012, 8 (3):e1002557 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid22396645en
dc.identifier.doi10.1371/journal.ppat.1002557en
dc.identifier.urihttp://hdl.handle.net/10033/603509en
dc.description.abstractVaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.en
dc.language.isoenen
dc.relation'info:eu-repo/grantAgreement/EC/FP7/'261466en
dc.rightsopenAccessen
dc.subject.meshAnimalsen
dc.subject.meshBioterrorismen
dc.subject.meshCD8-Positive T-Lymphocytesen
dc.subject.meshDisease Models, Animalen
dc.subject.meshHumansen
dc.subject.meshImmunity, Cellularen
dc.subject.meshMiceen
dc.subject.meshPore Forming Cytotoxic Proteinsen
dc.subject.meshSmallpoxen
dc.subject.meshSmallpox Vaccineen
dc.subject.meshVaccinationen
dc.subject.meshVaccines, Syntheticen
dc.subject.meshVaccinia virusen
dc.titleCritical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research, Braunschweig, and Hannover Medical School, Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

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