This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sofer-Podesta, C.
Right arrow Articles by Boyer, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sofer-Podesta, C.
Right arrow Articles by Boyer, J. L.

 Previous Article  |  Next Article 

Infection and Immunity, April 2009, p. 1561-1568, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.00856-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Adenovirus-Mediated Delivery of an Anti-V Antigen Monoclonal Antibody Protects Mice against a Lethal Yersinia pestis Challenge{triangledown}

Carolina Sofer-Podesta,1 John Ang,1 Neil R. Hackett,1 Svetlana Senina,2 David Perlin,2 Ronald G. Crystal,1* and Julie L. Boyer1

Department of Genetic Medicine, Weill Cornell Medical College, New York, New York,1 Public Health Research Institute, Newark, New Jersey2

Received 11 July 2008/ Returned for modification 29 September 2008/ Accepted 12 December 2008

Pneumonic plague, caused by inhalation of Yersinia pestis, represents a major bioterrorism threat for which no vaccine is available. Based on the knowledge that genetic delivery of monoclonal antibodies (MAbs) with adenovirus (Ad) gene transfer vectors results in rapid, high-level antibody expression, we evaluated the hypothesis that Ad-mediated delivery of a neutralizing antibody directed against the Y. pestis V antigen would protect mice against a Y. pestis challenge. MAbs specific for the Y. pestis V antigen were generated, and the most effective in protecting mice against a lethal intranasal Y. pestis challenge was chosen for further study. The coding sequences for the heavy and light chains were isolated from the corresponding hybridoma and inserted into a replication-defective serotype 5 human Ad gene transfer vector (Ad{alpha}V). Western analysis of Ad{alpha}V-infected cell supernatants demonstrated completely assembled antibodies reactive with V antigen. Following Ad{alpha}V administration to mice, high levels of anti-V antigen antibody titers were detectable as early as 1 day postadministration, peaked by day 3, and remained detectable through a 12-week time course. When animals that received Ad{alpha}V were challenged with Y. pestis at day 4 post-Ad{alpha}V administration, 80% of the animals were protected, while 0% of control animals survived (P < 0.01). Ad-mediated delivery of a V antigen-neutralizing antibody is an effective therapy against plague in experimental animals and could be developed as a rapidly acting antiplague therapeutic.

* Corresponding author. Mailing address: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, P.O. Box 96, New York, NY 10065. Phone: (646) 962-4363. Fax: (646) 962-0220. E-mail: geneticmedicine{at}med.cornell.edu

{triangledown} Published ahead of print on 5 January 2009.

Editor: R. P. Morrison

Infection and Immunity, April 2009, p. 1561-1568, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.00856-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»