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.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Sofer-Podesta C,Ang J,Hackett NR,Senina S,Perlin D,Crystal RG,Boyer JLdoi
10.1128/IAI.00856-08subject
Has Abstractpub_date
2009-04-01 00:00:00pages
1561-8issue
4eissn
0019-9567issn
1098-5522pii
IAI.00856-08journal_volume
77pub_type
杂志文章abstract::Our previous studies demonstrated that Mycobacterium bovis bacillus Calmette-Guérin (BCG) can directly interact with human NK cells and induce the proliferation, gamma interferon production, and cytotoxic activity of such cells without the need for accessory cells. Thus, the aim of the present study was to identify th...
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.36.1.320-324.1982
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journal_title:Infection and immunity
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doi:10.1128/IAI.60.9.3916-3917.1992
更新日期:1992-09-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.62.7.2715-2721.1994
更新日期:1994-07-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1128/IAI.66.7.3443-3446.1998
更新日期:1998-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.12.5078-5084.1992
更新日期:1992-12-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.13.3.982-986.1976
更新日期:1976-03-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.36.3.885-892.1982
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doi:10.1128/IAI.72.8.4603-4611.2004
更新日期:2004-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.11.2715-2720.1987
更新日期:1987-11-01 00:00:00
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更新日期:2003-07-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.17.2.356-360.1977
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journal_title:Infection and immunity
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更新日期:1971-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00160-20
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2001-08-01 00:00:00
abstract::Porphyromonas gingivalis is a periodontal pathogen capable of invading primary cultures of normal human gingival epithelial cells (NHGEC). Involvement of P. gingivalis fimbriae in the invasion process was examined. Purified P. gingivalis 33277 fimbriae blocked invasion of this organism into NHGEC in a dose-dependent m...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.65.1.313-316.1997
更新日期:1997-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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