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Infection and Immunity, February 2006, p. 1009-1015, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1009-1015.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cytokine Response and Survival of Mice Immunized with an Adenovirus Expressing Bacillus anthracis Protective Antigen Domain 4

Michael J. McConnell,1,2 Philip C. Hanna,2 and Michael J. Imperiale1,2*

Department of Microbiology and Immunology,2 Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-09421

Received 26 September 2005/ Returned for modification 29 October 2005/ Accepted 5 November 2005

Adenovirus vectors are promising for use in vaccinating against potential agents of bioterrorism and emerging infections because of their proven safety in humans and their ability to elicit rapid immune responses. Here, we describe the construction and evaluation of an adenovirus vaccine expressing domain 4 of Bacillus anthracis protective antigen, Ad.D4. Ad.D4 elicited antibodies to protective antigen 14 days after a single intramuscular injection, which were further increased upon boosting. Furthermore, two doses of Ad.D4 4 weeks apart were sufficient to protect 67% of mice from toxin challenge. Additionally, we have characterized the release of inflammatory cytokines from vaccinated mice after lethal-toxin challenge. We demonstrate that interleukin 1ß (IL-1ß) levels in mice that survive lethal toxin challenge are similar to levels in nonsurvivors and that IL-6 levels are higher in survivors than in nonsurvivors. These findings suggest that lethal-toxin-mediated death may not be a direct result of inflammatory-cytokine release.

* Corresponding author. Mailing address: University of Michigan Medical School, 6304 Cancer Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0942. Phone: (734) 763-9162. Fax: (734) 615-6560. E-mail: imperial{at}umich.edu.

Editor: J. T. Barbieri

Infection and Immunity, February 2006, p. 1009-1015, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1009-1015.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thomas, J. M., Moen, S. T., Gnade, B. T., Vargas-Inchaustegui, D. A., Foltz, S. M., Suarez, G., Heidner, H. W., Konig, R., Chopra, A. K., Peterson, J. W. (2009). Recombinant Sindbis Virus Vectors Designed To Express Protective Antigen of Bacillus anthracis Protect Animals from Anthrax and Display Synergy with Ciprofloxacin. CVI 16: 1696-1699 [Abstract] [Full Text]  
  • Abboud, N., Casadevall, A. (2008). Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background. CVI 15: 1115-1123 [Abstract] [Full Text]  
  • McConnell, M. J., Danthinne, X., Imperiale, M. J. (2006). Characterization of a permissive epitope insertion site in adenovirus hexon.. J. Virol. 80: 5361-5370 [Abstract] [Full Text]  


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