Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

Sun, Yaping; Dong, Wenjuan; Tian, Lei; Rao, Youliang; Qin, Chao; Jaramillo, Sierra A.; Settles, Erik W.; Ma, Shoubao; Zhang, Jianying; Yu, Kang; Xu, Bo; Yan, Jiazhuo; Ma, Rui; Li, Zhuo; Dadwal, Sanjeet S.; Barker, Bridget M.; Keim, Paul S.; Feng, Pinghui; Caligiuri, Michael A.; Yu, Jianhua

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response. One Sentence Summary A herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression