Vaccinia virus (VV) has been utilized in oncolytic virotherapy, but it risks a host antiviral immune response. VV has an extracellular enveloped virus (EEV) form consisting of a normal virion covered with a host-derived outer membrane that enables its spread via circulation while evading host immune mechanisms. However, the immune resistance of EEV is only partial, owing to expression of the surface protein B5R, which has four short consensus repeat (SCR) domains that are targeted by host immune factors. To engineer a more effective virus for oncolytic virotherapy, we developed an enhanced immune-evading oncolytic VV by removing the SCRs from the attenuated strain LC16mO. Although deletion of only the SCRs preserved viral replication, progeny production, and oncolytic activity, deletion of whole B5R led to attenuation of the virus. Importantly, SCR-deleted EEV had higher neutralization resistance than did B5R-wild-type EEV against VV-immunized animal serum; moreover, it retained oncolytic function, thereby prolonging the survival of tumor-bearing mice treated with anti-VV antibody. These results demonstrate that partial SCR deletion increases neutralization escape without affecting the oncolytic potency of VV, making it useful for the treatment of tumors under the anti-virus antibody existence.

牛痘病毒（VV）已被用于溶瘤病毒疗法，但它具有宿主抗病毒免疫反应的风险。VV具有细胞外被膜病毒（EEV）形式，由正常病毒体组成，该病毒体被宿主衍生的外膜覆盖，可使其通过循环传播而逃避宿主免疫机制。但是，由于表面蛋白B5R的表达，EEV的免疫抗性仅是部分的，该蛋白具有四个短的共有重复序列（SCR）结构域，这些结构域是宿主免疫因子靶向的。为了设计出更有效的溶瘤病毒疗法病毒，我们通过从减毒菌株LC16mO中去除SCR，开发了增强的免疫逃避溶瘤病毒VV。尽管仅SCR的删除保留了病毒复制，后代生产和溶瘤活性，但整个B5R的删除导致病毒减毒。重要的，SCR缺失的EEV对VV免疫动物血清的抵抗力比B5R野生型EEV高。而且，它保留了溶瘤功能，从而延长了用抗VV抗体治疗的荷瘤小鼠的存活。这些结果证明，部分SCR缺失增加中和逃逸而不影响VV的溶瘤能力，使其可用于抗病毒抗体存在下的肿瘤治疗。