炭疽毒素中和试验中单克隆抗体特定组合的分析及其协同作用。
Analysis of defined combinations of monoclonal antibodies in anthrax toxin neutralization assays and their synergistic action.
作者信息
Ngundi Miriam M, Meade Bruce D, Little Stephen F, Quinn Conrad P, Corbett Cindi R, Brady Rebecca A, Burns Drusilla L
机构信息
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
出版信息
Clin Vaccine Immunol. 2012 May;19(5):731-9. doi: 10.1128/CVI.05714-11. Epub 2012 Mar 21.
Abstract
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.
摘要
抗炭疽毒素保护性抗原（PA）成分的抗体在预防炭疽芽孢杆菌引起的疾病中发挥着重要作用。在本研究中，我们在细胞培养试验中检测了特定组合的PA特异性单克隆抗体中和炭疽毒素的能力。根据所检测的特定抗体组合和所使用的特定试验，我们观察到了抗体的相加、协同和拮抗作用。我们对协同性毒素中和抗体相互作用进行了更详细的研究。我们发现，一种可导致抗体协同作用的机制是一种抗体桥接PA单体，从而使第二种抗体产生二价结合。这些结果可能有助于针对炭疽的新型疫苗和抗体疗法的优化设计。
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