Adenovirus-mediated delivery of an anti-v antigen monoclonal antibody protects mice against a lethal yersinia pestis challenge Carolina sofer-podesta

John Ang, Neil R. Hackett, Svetlana Senina, David Perlin, Ronald Crystal, Julie L. Boyer

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27 Citations (Scopus)

Abstract

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 (AdαV). Western analysis of AdαV-infected cell supernatants demonstrated completely assembled antibodies reactive with V antigen. Following AdαV 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 AdαV were challenged with Y. pestis at day 4 post-AdaV 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.

Original languageEnglish
Pages (from-to)1561-1568
Number of pages8
JournalInfection and Immunity
Volume77
Issue number4
DOIs
Publication statusPublished - 1 Apr 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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