The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody.

中文翻译：

---

补体抑制使得在存在抗病毒抗体的情况下能够递送LCMV糖蛋白假型病毒的肿瘤。

治疗性病毒（例如溶瘤病毒或疫苗）的全身递送受到中和抗体产生的限制。虽然以前用淋巴细胞性脉络膜脑膜炎病毒糖蛋白对弹状病毒进行假分型，但可以在小鼠中进行多轮分娩，但这种策略尚未转化为其他动物模型。首次，我们提供了实验证据，证明针对淋巴细胞脉络膜脑膜炎病毒糖蛋白的抗体通过经典途径的激活介导了强大的补体依赖性病毒中和作用。我们表明，该表型可以利用在补体调节剂的作用下，在面对中和抗体的Fischer大鼠模型中，传递与淋巴细胞性脉络膜脑膜炎病毒糖蛋白假型化的马拉巴病毒。