ELISA units, IgG subclass ratio and avidity determined functional activity of mouse anti-Pfs230 antibodies judged by a standard membrane-feeding assay with Plasmodium falciparum
ELISA units, IgG subclass ratio and avidity determined functional activity of mouse anti-Pfs230 antibodies judged by a standard membrane-feeding assay with Plasmodium falciparum
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DOI：
10.1016/j.vaccine.2019.02.071
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发表时间：
2019-04-03
期刊：
影响因子：
5.5
通讯作者：
Long, Carole A.
中科院分区：
文献类型：
--
作者：
Miura, Kazutoyo;Deng, Bingbing;Long, Carole A.
标准膜喂养试验（SMFA）是一种功能性试验，已用于为恶性疟原虫疟疾传播阻断疫苗（TBV）的开发提供信息。对于Pfs 230，TBV发展的主要靶抗原，一些研究已经测试了连续稀释的单一抗Pfs 230多克隆或单克隆抗体（每个研究一种抗体），并显示出剂量依赖性反应。此外，已有报道称，在补体存在下，抗Pfs 230多克隆和单克隆抗体的SMFA活性增强。然而，尚未对多个样本进行分析，并通过SMFA评价了抗Pfs 230抗体滴度、IgG亚类谱和亲合力对降低传播活性（TRA）的影响。在本报告中，评估了来自5项不同小鼠免疫研究的共计39种独特抗Pfs 230 IgG的ELISA单位（EU）、IgG 2/IgG 1比和亲合力（ELISA法）以及功能性（%传播减少活性，%TRA）（SMFA法）。使用Alhydrogel或Montanide ISA 720佐剂，用单独的Pfs 230、与CRM 197缀合的Pfs 230或未缀合的Pfs 230和CRM 197蛋白的混合物免疫小鼠。在所有研究中，Pfs 230抗原均来自同一来源。对于抗Pfs 230 IgG，EU和%TRA之间存在显著相关性（通过斯皮尔曼秩检验，p < 0.0001）。值得注意的是，多元线性回归分析显示，在调整EU后，IgG 2/IgG 1比值和亲合力均显著影响%TRA（p = 0.003至p = 0.014，取决于模型）。结果表明，除了抗体滴度，IgG 2/IgG 1比和亲合力应分别进行评估，以预测未来疫苗开发的抗Pfs 230抗体的生物活性。(C)2019由Elsevier Ltd.出版
The standard membrane-feeding assay (SMFA) is a functional assay that has been used to inform the development of transmission-blocking vaccines (TBV) against Plasmodium falciparum malaria. For Pfs230, a lead target antigen for TBV development, a few studies have tested either a single anti-Pfs230 poly-clonal or monoclonal antibody (one antibody per study) at serial dilutions and showed a dose-dependent response. Further, there have been reports that the SMFA activity of anti-Pfs230 poly-clonal and monoclonal antibodies were enhanced in the presence of complement. However, no analysis has been performed with multiple samples, and the impact of anti-Pfs230 antibody titers, IgG subclass profile and avidity were evaluated together in relation to transmission-reducing activity (TRA) by SMFA. In this report, a total of 39 unique anti-Pfs230 IgGs from five different mouse immunization studies were assessed for their ELISA units (EU), IgG2/IgG1 ratio and avidity by ELISA, and the functionality (% transmission-reducing activity, %TRA) by SMFA. The mice were immunized with Pfs230 alone, Pfs230 conjugated to CRM197, or a mixture of unconjugated Pfs230 and CRM 197 proteins using Alhydrogel or Montanide ISA720 adjuvants. In all studies, the Pfs230 antigen was from the same source. There was a significant correlation between EU and %TRA (p < 0.0001 by a Spearman rank test) for the anti-Pfs230 lgGs. Notably, multiple linear regression analyses showed that both IgG2/IgG1 ratio and avidity significantly affected %TRA (p = 0.003 to p = 0.014, depending on the models) after adjusting for EU. The results suggest that in addition to antibody titers, IgG2/IgG1 ratio and avidity should each be evaluated to predict the biological activity of anti-Pfs230 antibodies for future vaccine development. (C) 2019 Published by Elsevier Ltd.