Anthrax Vaccine-Induced Antibodies Provide Cross-Species Prediction of Survival to Aerosol Challenge
Anthrax Vaccine-Induced Antibodies Provide Cross-Species Prediction of Survival to Aerosol Challenge
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DOI：
10.1126/scitranslmed.3004073
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发表时间：
2012-09-12
影响因子：
17.1
通讯作者：
Nuzum, Edwin O.
中科院分区：
文献类型：
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作者：
Fay, Michael P.;Follmann, Dean A.;Nuzum, Edwin O.
由于评估疫苗对炭疽的有效性的临床试验既不符合伦理，也不可行，新的炭疽疫苗的许可很可能涉及美国食品和药物管理局(Food and Drug Administration，简称FDA)的“动物规则”，这是一套法规，允许仅根据动物的疗效数据以及动物和人类的免疫原性和安全性数据来批准产品。美国政府资助的动物研究表明，炭疽疫苗在各种环境下都有效果。我们检查了其中21项研究的数据，以确定基于致死毒素中和活性分析(TNA)的免疫学桥梁是否可以预测在物种和属内以及跨物种和属之间抵抗吸入性炭疽挑战的存活率。这21项研究被分成11个不同的环境，每个环境都有相同的动物种类、疫苗类型和配方、疫苗接种计划、TNA测量时间和挑战时间。Logistic回归模型确定了疫苗稀释量和TNA对生存预测的贡献。在大多数情况下，仅使用TNA的Logistic模型解释了额外包括剂量的模型的75%以上的生存效应。使用TNA的跨物种生存预测与实际生存进行了比较，结果显示有很好的一致性(Cohen‘s kappa从0.55到0.78)。在一项研究设计中，食蟹猴数据预测猕猴存活率为78.6%(实际存活率为83.0%)，兔子存活率为72.6%(实际存活率为64.6%)。这些数据支持使用TNA作为物种之间的免疫学桥梁来推断动物数据，以预测炭疽疫苗在人类中的有效性。
Because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the Food and Drug Administration's "Animal Rule," a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. U.S. government-sponsored animal studies have shown anthrax vaccine efficacy in a variety of settings. We examined data from 21 of those studies to determine whether an immunological bridge based on lethal toxin neutralization activity assay (TNA) can predict survival against an inhalation anthrax challenge within and across species and genera. The 21 studies were classified into 11 different settings, each of which had the same animal species, vaccine type and formulation, vaccination schedule, time of TNA measurement, and challenge time. Logistic regression models determined the contribution of vaccine dilution dose and TNA on prediction of survival. For most settings, logistic models using only TNA explained more than 75% of the survival effect of the models with dose additionally included. Cross-species survival predictions using TNA were compared to the actual survival and shown to have good agreement (Cohen's kappa ranged from 0.55 to 0.78). In one study design, cynomolgus macaque data predicted 78.6% survival in rhesus macaques (actual survival, 83.0%) and 72.6% in rabbits (actual survival, 64.6%). These data add support for the use of TNA as an immunological bridge between species to extrapolate data in animals to predict anthrax vaccine effectiveness in humans.