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

Research output: Contribution to journalArticle

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

Fingerprint

Yersinia pestis
Adenoviridae
Monoclonal Antibodies
Antigens
Plague
Neutralizing Antibodies
Antibodies
Bioterrorism
Human Adenoviruses
Hybridomas
Inhalation
Genes
Vaccines
Light
Therapeutics

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Adenovirus-mediated delivery of an anti-v antigen monoclonal antibody protects mice against a lethal yersinia pestis challenge Carolina sofer-podesta. / Ang, John; Hackett, Neil R.; Senina, Svetlana; Perlin, David; Crystal, Ronald; Boyer, Julie L.

In: Infection and Immunity, Vol. 77, No. 4, 01.04.2009, p. 1561-1568.

Research output: Contribution to journalArticle

Ang, John ; Hackett, Neil R. ; Senina, Svetlana ; Perlin, David ; Crystal, Ronald ; Boyer, Julie L. / Adenovirus-mediated delivery of an anti-v antigen monoclonal antibody protects mice against a lethal yersinia pestis challenge Carolina sofer-podesta. In: Infection and Immunity. 2009 ; Vol. 77, No. 4. pp. 1561-1568.
@article{9ee6ab4af54e4c0eb5bd9bf09b925f17,
title = "Adenovirus-mediated delivery of an anti-v antigen monoclonal antibody protects mice against a lethal yersinia pestis challenge ∇ Carolina sofer-podesta",
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.",
author = "John Ang and Hackett, {Neil R.} and Svetlana Senina and David Perlin and Ronald Crystal and Boyer, {Julie L.}",
year = "2009",
month = "4",
day = "1",
doi = "10.1128/IAI.00856-08",
language = "English",
volume = "77",
pages = "1561--1568",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Adenovirus-mediated delivery of an anti-v antigen monoclonal antibody protects mice against a lethal yersinia pestis challenge ∇ Carolina sofer-podesta

AU - Ang, John

AU - Hackett, Neil R.

AU - Senina, Svetlana

AU - Perlin, David

AU - Crystal, Ronald

AU - Boyer, Julie L.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=63149166807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63149166807&partnerID=8YFLogxK

U2 - 10.1128/IAI.00856-08

DO - 10.1128/IAI.00856-08

M3 - Article

VL - 77

SP - 1561

EP - 1568

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

ER -