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首页> 外文期刊>Infection and immunity >Characterization of a Lipopolysaccharide-Targeted Monoclonal Antibody and Its Variable Fragments as Candidates for Prophylaxis against the Obligate Intracellular Bacterial Pathogen Coxiella burnetii
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Characterization of a Lipopolysaccharide-Targeted Monoclonal Antibody and Its Variable Fragments as Candidates for Prophylaxis against the Obligate Intracellular Bacterial Pathogen Coxiella burnetii

机译：脂多糖靶向的单克隆抗体及其可变片段作为预防专攻细胞内细菌性病原体柯氏杆菌的候选者的表征

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Our previous study demonstrated that treatment of Coxiella burnetii with the phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4 significantly inhibited C. burnetii infection in mice, suggesting that 1E4 is a protective MAb. To determine whether passive transfer of antibodies (Abs) can provide protection against C. burnetii natural infection, we examined if passive transfer of 1E4 would protect SCID mice against C. burnetii aerosol infection. The results indicated that 1E4 conferred significant protection against aerosolized C. burnetii, suggesting that 1E4 may be useful for preventing C. burnetii natural infection. To further understand the mechanisms of 1E4-mediated protection and to test the possibility of using humanized 1E4 to prevent C. burnetii infection, we examined whether the Fab fragment of 1E4 (Fab1E4), a recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibit C. burnetii infection. The results indicated that Fab1E4, muscFv1E4, and huscFv1E4 were able to inhibit C. burnetii infection in mice but that their ability to inhibit C. burnetii infection was lower than that of 1E4. In addition, treatment of C. burnetii with Fab1E4, muscFv1E4, or huscFv1E4 can block C. burnetii infection of macrophages. Interestingly, treatment of C. burnetii with huscFv1E4 can significantly reduce C. burnetii infectivity in human macrophages. This report provides the first evidence to demonstrate that the humanized variable fragments of an LPS-specific MAb can neutralize C. burnetii infection and appears to be a promising step toward the potential use of a humanized MAb as emergency prophylaxis against C. burnetii exposure.
机译：我们先前的研究表明，以I相脂多糖（PI-LPS）靶向的单克隆抗体（MAb）1E4治疗柯氏杆菌可显着抑制小鼠梭状芽胞杆菌的感染，这表明1E4是一种保护性MAb。为了确定抗体（Abs）的被动转移是否可以提供抗伯氏梭菌自然感染的保护，我们检查了1E4的被动转移是否可以保护SCID小鼠免受伯氏梭菌气溶胶感染。结果表明1E4赋予了对气溶胶化的伯氏梭菌的显着保护，表明1E4可能对预防伯氏梭菌的自然感染有用。为了进一步了解1E4介导的保护机制并测试使用人源化1E4预防伯氏梭菌感染的可能性，我们检查了重组鼠单链可变片段（muscFv1E4）1E4的Fab片段（Fab1E4）是否存在，人源化单链可变片段（huscFv1E4）保留了1E4抑制伯氏梭菌感染的能力。结果表明，Fab1E4，muscFv1E4和huscFv1E4能够抑制小鼠的伯氏梭状芽胞杆菌感染，但它们抑制伯氏梭状芽胞杆菌感染的能力低于1E4。此外，用Fab1E4，muscFv1E4或huscFv1E4处理伯氏梭菌可以阻断巨噬细胞对伯氏梭菌的感染。有趣的是，用huscFv1E4处理伯氏梭状芽胞杆菌可显着降低人巨噬细胞中伯氏梭状芽胞杆菌的感染性。该报告提供了第一个证据，证明LPS特异性MAb的人源化可变片段可以中和伯氏梭状芽胞杆菌感染，并且似乎是朝着潜在使用人源化单克隆抗体作为对付伯氏梭状芽胞杆菌暴露的紧急预防的希望之路。

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