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

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 expressio...

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Bibliographic Details
Published in:Infection and Immunity 2009-04, Vol.77 (4), p.1561-1568
Main Authors: Sofer-Podesta, Carolina, Ang, John, Hackett, Neil R, Senina, Svetlana, Perlin, David, Crystal, Ronald G, Boyer, Julie L
Format: Article
Language:English
Subjects:
Adenovirus
Adenoviruses, Human - genetics
Animals
Antibodies, Bacterial - administration & dosage
Antibodies, Bacterial - genetics
Antibodies, Bacterial - immunology
Antibodies, Bacterial - therapeutic use
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Antigens, Bacterial - genetics
Antigens, Bacterial - immunology
Applied microbiology
Bacteriology
Biological and medical sciences
Female
Fundamental and applied biological sciences. Psychology
Genetic Vectors
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Microbial Immunity and Vaccines
Microbiology
Miscellaneous
Neutralization Tests
Plague - immunology
Plague - microbiology
Plague - mortality
Plague - prevention & control
Pore Forming Cytotoxic Proteins - genetics
Pore Forming Cytotoxic Proteins - immunology
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Virology
Yersinia pestis
Yersinia pestis - immunology
Yersinia pestis - pathogenicity
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Summary: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-AdαV 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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00856-08