Partial Deletion of Glycoprotein B5R Enhances Vaccinia Virus Neutralization Escape while Preserving Oncolytic Function

Abstract

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.

Generation of a Novel Oncolytic Vaccinia Virus Using the IHD-W Strain

“…27 It is also reported that partial deletion of the B5R gene increases EEV productivity, which can be applied to improve the efficacy of oncolytic vaccinia viruses. 28 In this study, we confirmed that the IHD-W strain harbors these distinct characteristics compared with other strains (Fig. 1).…”

Materials promoting viral gene delivery

“…[86][87][88] For example, introduction of unnatural amino acid residues such as azides on the capsid surface can give access to selective click chemistry. 89,90 Further, genetically modified viruses can enhance TE, 91,92 broaden the tropism, 63,93 enable fluorescent imaging, 85 escape neutralizing antibodies, 94,95 generate stimuli responsive vectors, 96 e.g. by light 97,98 or enzymes, 99 and target cells.…”

Power and Promise of Next-Generation Sequencing in Liquid Biopsies and Cancer Control

“…[124][125][126][127] An important application of cfDNA analysis is to guide treatment decisions, especially in targeted therapy. [128][129][130] For example, liquid biopsy to analyze EGFR mutations has been widely used to guide the use of epidermal growth factor receptor-tyrosine kinase inhibitors. 131 Many studies have demonstrated that targeted large-scale parallel sequencing can be used to identify cancer-related driver mutations in the cfDNA of patients with HCC.…”