SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus

Despite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.Instituto de BiotecnologíaFil: Alkayyal, Almohanad A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia SauditaFil: Alkayyal, Almohanad A. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFil: Ajina, Reham. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFil: Ajina, Reham. King Saud bin Abdulaziz University for Health Sciences. College of Applied Medical Sciences. Department of Clinical Laboratory Sciences; Arabia SauditaFil: Cacciabue, Marco Polo Domingo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Cacciabue, Marco Polo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cacciabue, Marco Polo Domingo. Universidad Nacional de Luján. Departamento de Ciencias Básicas; ArgentinaFil: Alkayyal, Aaesha A. Taibah University. College of Medicine; Arabia SauditaFil: Saeedi, Nizar H. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia SauditaFil: Hussain Alshehry, Taofik. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia SauditaFil: Kaboha, Feras. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia SauditaFil: Alotaibi, Mohammed A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia SauditaFil: Alotaibi, Mohammed A. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia SauditaFil: Zaidan, Nada. King Abdulaziz City for Science and Technology. Joint Centers of Excellence Program. 8King Abdulaziz City for Science and Technology-Brigham and Women's Hospital (KACST-BWH) Centre of Excellence for Biomedicine; Arabia SauditaFil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Center for Stem Cell and Translational Immunotherapy (CSTI); Estados UnidosFil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Department of Neurosurgery; Estados UnidosFil: Shah, Khalid. Harvard University. Harvard Stem Cell Institute; Estados UnidosFil: Alroqi, Fayhan. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFil: Alroqi, Fayhan. Ministry of the National Guard. Department of Immunology; Arabia SauditaFil: Alroqi, Fayhan. King Saud bin Abdulaziz University for Health Sciences. Faculty of Medicine; Arabia SauditaFil: Bakur Mahmoud, Ahmad. Taibah University. College of Applied Medical Sciences; Arabia SauditaFil: Bakur Mahmoud, Ahmad. Taibah University. Strategic Research and Innovation Laboratories; Arabia SauditaFil: Bakur Mahmoud, Ahmad. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudit

Repurposing the oncolytic virus VSV∆51M as a COVID-19 vaccine

The coronavirus disease 2019 (COVID-19) pandemic imposes an urgent and continued need for the development of safe and cost-effective vaccines to induce preventive responses for limiting major outbreaks around the world. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we repurposed the VSV∆51M oncolytic virus platform to express the spike receptor-binding domain (RBD) antigen. In this study, we report the development and characterization of the VSV∆51M-RBD vaccine. Our findings demonstrate successful expression of the RBD gene by the VSV∆51M-RBD virus, inducing anti-RBD responses without attenuating the virus. Moreover, the VSV∆51M-RBD vaccine exhibited safety, immunogenicity, and the potential to serve as a safe and effective alternative or complementary platform to current COVID-19 vaccines