Adenovirus-mediated delivery of an anti-V antigen monoclonal antibody protects mice against a lethal Yersinia pestis challenge.
| Publication Type | Academic Article |
| Authors | Sofer-Podesta C, Ang J, Hackett N, Senina S, Perlin D, Crystal R, Boyer J |
| Journal | Infect Immun |
| Volume | 77 |
| Issue | 4 |
| Pagination | 1561-8 |
| Date Published | 01/05/2009 |
| ISSN | 1098-5522 |
| Keywords | 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. |
| DOI | 10.1128/IAI.00856-08 |
| PubMed ID | 19124600 |
| PubMed Central ID | PMC2663162 |