Survival of recombinant monoclonal and naturally-occurring human milk immunoglobulins A and G specific to respiratory syncytial virus F protein across simulated human infant gastrointestinal digestion.
Survival of recombinant monoclonal and naturally-occurring human milk immunoglobulins A and G specific to respiratory syncytial virus F protein across simulated human infant gastrointestinal digestion.
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DOI：
10.1016/j.jff.2020.104115
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发表时间：
2020-10
影响因子：
5.6
通讯作者：
Dallas DC
中科院分区：
文献类型：
--
作者：
Lueangsakulthai J;Sah BNP;Scottoline BP;Dallas DC
天然存在的抗体比单克隆抗体更耐降解。单克隆sIgA比IgG和伊加更耐降解。单克隆抗体可能需要以更高的剂量提供，以补偿消化损失。为了帮助合理设计用于口服给药的抗体，我们检查了具有相同可变序列的不同同种型（IgG、伊加和sIgA）如何影响消化过程中的抗体稳定性。我们通过经验证的RSV F蛋白ELISA，在体外婴儿消化模型的胃和肠阶段，比较了人乳中加标的重组帕利珠单抗（IgG 1）以及重组伊加和sIgA形式帕利珠单抗的降解与来自4名供体的人乳中天然存在的抗呼吸道合胞病毒（RSV）sIgA/伊加和IgG的降解。完全模拟胃肠道消化后，帕利珠单抗IgG和伊加形式的稳定性低于sIgA形式：帕利珠单抗IgG、伊加和sIgA在完全模拟胃肠道消化中分别降低55%、48%和28%。天然存在的RSV F蛋白特异性IgG在整个消化过程中是稳定的，而天然存在的sIgA/伊加在胃阶段是稳定的，但在模拟消化的肠阶段降低了33%。
Naturally-occurring antibodies were more resistant to degradation than monoclonal antibodies. Monoclonal sIgA was more resistant to degradation than IgG and IgA. Monoclonal antibodies may need to be provided at a higher dose to compensate for digestive losses. To help rationally design an antibody for oral administration, we examined how different isotypes (IgG, IgA and sIgA) with the same variable sequence affect antibody stability across digestion. We compared the degradation of recombinant palivizumab (IgG1), and recombinant IgA and sIgA versions of palivizumab spiked in human milk to the degradation of naturally-occurring anti-respiratory syncytial virus (RSV) sIgA/IgA and IgG in human milk from four donors across gastric and intestinal phases of an in vitro model of infant digestion via a validated RSV F protein ELISA. Palivizumab IgG and IgA formats were less stable than the sIgA version after complete simulated gastrointestinal digestion: palivizumab IgG, IgA and sIgA decreased across complete simulated gastrointestinal digestion by 55%, 48% and 28%, respectively. Naturally-occurring RSV F protein-specific IgG was stable across digestion, whereas naturally-occurring sIgA/IgA was stable in the gastric phase but decreased 33% in the intestinal phase of simulated digestion.
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