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Journal of Virology, July 2007, p. 7022-7033, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02654-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Direct Comparison of Antigen Production and Induction of Apoptosis by Canarypox Virus- and Modified Vaccinia Virus Ankara-Human Immunodeficiency Virus Vaccine Vectors{triangledown}

Xiugen Zhang,1 Farah Cassis-Ghavami,2 Mike Eller,3 Jeff Currier,3 Bonnie M. Slike,3 Xuemin Chen,1 James Tartaglia,4 Mary Marovich,3 and Paul Spearman1*

Departments of Pediatrics and Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia,1 Department of Pediatrics, Vanderbilt University, Nashville, Tennessee,2 U.S. Military HIV Research Program, Rockville, Maryland,3 Sanofi Pasteur, Toronto, Ontario, Canada4

Received 30 November 2006/ Accepted 29 March 2007

Recombinant poxvirus vectors are undergoing intensive evaluation as vaccine candidates for a variety of infectious pathogens. Avipoxviruses, such as canarypox virus, are replication deficient in mammalian cells by virtue of a poorly understood species-specific restriction. Highly attenuated vaccinia virus strains such as modified vaccinia virus Ankara (MVA) are similarly unable to complete replication in most mammalian cells but have an abortive-late phenotype, in that the block to replication occurs post-virus-specific DNA replication. In this study, an identical expression cassette for human immunodeficiency virus gag, pro, and env coding sequences was placed in canarypox virus and MVA vector backbones in order to directly compare vector-borne expression and to analyze differences in vector-host cell interactions. Antigen production by recombinant MVA was shown to be greater than that from recombinant canarypox virus in the mammalian cell lines and in the primary human cells tested. This observation was primarily due to a longer duration of antigen production in recombinant MVA-infected cells. Apoptosis induction was found to be more profound with the empty canarypox virus vector than with MVA. Remarkably, however, the inclusion of a gag/pro/env expression cassette altered the kinetics of apoptosis induction in recombinant MVA-infected cells to levels equal to those found in canarypox virus-infected cells. Antigen production by MVA was noted to be greater in human dendritic cells and resulted in enhanced T-cell stimulation in an in vitro antigen presentation assay. These results reveal differences in poxvirus vector-host cell interactions that should be relevant to their use as immunization vehicles.

* Corresponding author. Mailing address: Departments of Pediatrics and Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 727-5642. Fax: (404) 727-8249. E-mail: paul.spearman{at}emory.edu

{triangledown} Published ahead of print on 4 April 2007.

Journal of Virology, July 2007, p. 7022-7033, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02654-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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