An armed anti-immunoglobulin light chain nanobody protects mice against influenza A and B infections.
An armed anti-immunoglobulin light chain nanobody protects mice against influenza A and B infections.
复制标题
武装抗免疫球蛋白轻链纳米抗体可保护小鼠免受甲型和乙型流感病毒感染。
DOI：
10.1126/sciimmunol.adg9459
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发表时间：
2023
影响因子：
24.8
通讯作者：
Ploegh,HiddeL
中科院分区：
文献类型：
--
作者：
Liu,Xin;Balligand,Thomas;Carpenet,Claire;Ploegh,HiddeL
免疫系统清除病原体入侵者，如病毒和细菌。为了将免疫效应器招募到病毒感染的细胞中，我们将一个小分子，流感神经氨酸酶抑制剂扎那米韦连接到一个识别小鼠免疫球蛋白kappa轻链的纳米体上。该加合物旨在通过与循环中更大的免疫球蛋白形成络合物来延长扎那米韦的半衰期。扎那米韦部分针对病毒感染细胞的加合物，而抗kappa成分同时提供特异性不确定的所有同种类型的多克隆免疫球蛋白。抗体依赖细胞介导的细胞毒和补体依赖的细胞毒的激活促进了流感神经氨酸酶阳性细胞的消除。单剂这种结合物可以保护小鼠免受甲型或乙型流感病毒的感染，即使在感染致死剂量的病毒几天后给药也是有效的。在没有循环免疫球蛋白的情况下，我们没有观察到加合物对体内的保护作用。因此，这里描述的结合物类型可同时应用于抗流感预防和治疗。
The immune system eliminates pathogen intruders such as viruses and bacteria. To recruit immune effectors to virus-infected cells, we conjugated a small molecule, the influenza neuraminidase inhibitor zanamivir, to a nanobody that recognizes the kappa light chains of mouse immunoglobulins. This adduct was designed to achieve half-life extension of zanamivir through complex formation with the much-larger immunoglobulins in the circulation. The zanamivir moiety targets the adduct to virus-infected cells, whereas the anti-kappa component simultaneously delivers polyclonal immunoglobulins of indeterminate specificity and all isotypes. Activation of antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity promoted elimination of influenza neuraminidase-positive cells. A single dose of the conjugate protected mice against influenza A or B viruses and was effective even when given several days after infection with a lethal dose of virus. In the absence of circulating immunoglobulins, we observed no in vivo protection from the adduct. The type of conjugates described here may thus find application for both anti-influenza prophylaxis and therapy.