HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Staib, C. Articles by Sutter, G. Search for Related Content PubMed PubMed Citation Articles by Staib, C. Articles by Sutter, G. Agricola Articles by Staib, C. Articles by Sutter, G.

Inactivation of the viral interleukin 1 receptor improves CD8⁺ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara

¹ GSF Institute of Molecular Virology and Institute of Virology, Technical University of Munich, Trogerstrasse 4b, 81675 München, Germany
² Department of Virology, Paul-Ehrlich-Institute, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany

Correspondence
Gerd Sutter
sutge{at}pei.de

Interleukin 1 (IL1) is an important regulator of inflammatory responses and contributes to host immune defence against infection. Vaccinia virus encodes a viral soluble IL1 receptor (IL1R), which modulates the acute-phase host response to infection and might influence the induction of immune responses against virus-associated antigens. Here, modified vaccinia virus Ankara (MVA) mutants defective in IL1R production were produced by insertion of selectable marker gene sequences that precisely deleted the IL1R coding sequences from the MVA genome (MVA-IL1R). Analysis of MVA mutants indicated that deletion of the IL1R gene did not abrogate the formation of MVA progeny upon tissue culture propagation. After high-dose intranasal infection with MVA-IL1R, mice showed no signs of fever or other illness, suggesting that the avirulent phenotype remained preserved for MVA-IL1R. Following vaccination of mice, MVA-IL1R or non-mutated MVA induced similar acute-phase immune responses. Importantly, when monitored at the memory phase, significantly higher vaccinia virus-specific total CD8⁺ and HLA-A*0201-binding peptide epitope-specific T-cell responses were found after vaccination of HLA-A*0201-transgenic and non-transgenic mice with MVA-IL1R. Moreover, 4–6 months after vaccination, MVA-IL1R provided higher levels of protection against lethal respiratory challenge infection with virulent vaccinia virus strain Western Reserve compared with wild-type MVA. These data suggest that deletion of the viral IL1R gene may be considered a relevant approach to amplify the virus-specific CD8⁺ memory T-cell response and duration of protective immunity obtained after MVA vaccination.

This article has been cited by other articles:

				K. M. Sperling, A. Schwantes, C. Staib, B. S. Schnierle, and G. Sutter The Orthopoxvirus 68-Kilodalton Ankyrin-Like Protein Is Essential for DNA Replication and Complete Gene Expression of Modified Vaccinia Virus Ankara in Nonpermissive Human and Murine Cells J. Virol., June 15, 2009; 83(12): 6029 - 6038. [Abstract] [Full Text] [PDF]

				M. A. Fischer, D. C. Tscharke, K. B. Donohue, M. E. Truckenmiller, and C. C. Norbury Reduction of vector gene expression increases foreign antigen-specific CD8+ T-cell priming J. Gen. Virol., September 1, 2007; 88(9): 2378 - 2386. [Abstract] [Full Text] [PDF]

				C. Gubser, R. Goodbody, A. Ecker, G. Brady, L. A. J. O'Neill, N. Jacobs, and G. L. Smith Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence J. Gen. Virol., June 1, 2007; 88(6): 1667 - 1676. [Abstract] [Full Text] [PDF]

				C. Staib, Y. Suezer, S. Kisling, U. Kalinke, and G. Sutter Short-term, but not post-exposure, protection against lethal orthopoxvirus challenge after immunization with modified vaccinia virus Ankara. J. Gen. Virol., October 1, 2006; 87(Pt 10): 2917 - 2921. [Abstract] [Full Text] [PDF]

				R. Chavan, K. A. Marfatia, I. C. An, D. A. Garber, and M. B. Feinberg Expression of CCL20 and Granulocyte-Macrophage Colony-Stimulating Factor, but Not Flt3-L, from Modified Vaccinia Virus Ankara Enhances Antiviral Cellular and Humoral Immune Responses. J. Virol., August 1, 2006; 80(15): 7676 - 7687. [Abstract] [Full Text] [PDF]

				M. G. Cottingham, A. van Maurik, M. Zago, A. T. Newton, R. J. Anderson, M. K. Howard, J. Schneider, and M. A. Skinner Different Levels of Immunogenicity of Two Strains of Fowlpox Virus as Recombinant Vaccine Vectors Eliciting T-Cell Responses in Heterologous Prime-Boost Vaccination Strategies. Clin. Vaccine Immunol., July 1, 2006; 13(7): 747 - 757. [Abstract] [Full Text] [PDF]

				H. Ludwig, Y. Suezer, Z. Waibler, U. Kalinke, B. S. Schnierle, and G. Sutter Double-stranded RNA-binding protein E3 controls translation of viral intermediate RNA, marking an essential step in the life cycle of modified vaccinia virus Ankara. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1145 - 1155. [Abstract] [Full Text] [PDF]

				R. H. Clark, J. C. Kenyon, N. W. Bartlett, D. C. Tscharke, and G. L. Smith Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy J. Gen. Virol., January 1, 2006; 87(1): 29 - 38. [Abstract] [Full Text] [PDF]

				L. Jing, T. M. Chong, C. L. McClurkan, J. Huang, B. T. Story, and D. M. Koelle Diversity in the Acute CD8 T Cell Response to Vaccinia Virus in Humans J. Immunol., December 1, 2005; 175(11): 7550 - 7559. [Abstract] [Full Text] [PDF]