Adenovirus-mediated delivery of an anti-V antigen monoclonal antibody protects mice against a lethal Yersinia pestis challenge. Academic Article uri icon

Overview

MeSH

  • Animals
  • Female
  • Genetic Vectors
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neutralization Tests

MeSH Major

  • Adenoviruses, Human
  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • Plague
  • Pore Forming Cytotoxic Proteins
  • Yersinia pestis

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

publication date

  • April 2009

has subject area

  • Adenoviruses, Human
  • Animals
  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • Female
  • Genetic Vectors
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Plague
  • Pore Forming Cytotoxic Proteins
  • Yersinia pestis

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2663162

Digital Object Identifier (DOI)

  • 10.1128/IAI.00856-08

PubMed ID

  • 19124600

Additional Document Info

start page

  • 1561

end page

  • 1568

volume

  • 77

number

  • 4