Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action

被引:14
|
作者
Ngundi, Miriam M. [1 ]
Meade, Bruce D. [3 ]
Little, Stephen F. [2 ]
Quinn, Conrad P. [4 ]
Corbett, Cindi R. [5 ]
Brady, Rebecca A. [1 ]
Burns, Drusilla L. [1 ]
机构
[1] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA
[2] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA
[3] Meade Biol, Hillsborough, NC USA
[4] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA
[5] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
关键词
PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; LETHAL TOXIN; IN-VITRO; INHALATIONAL ANTHRAX; RHESUS MACAQUES; FC-RECEPTORS; GUINEA-PIGS; VACCINE; IMMUNITY;
D O I
10.1128/CVI.05714-11
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Antibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused by Bacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax.
引用
收藏
页码:731 / 739
页数:9
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