Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models

• DOI: 10.1016/j.vaccine.2021.05.098
• Publication Date: 2021-06-01T03:14:47Z
• Authors: Ayan Dey; T.M. Chozhavel Ra...; Harish Chandra; Hari P.R. Pericherla; Sanjeev Kumar; Huzaifa S. Choonia; Mayank Bajpai; Arun K. Singh; Anuradha Sinha; Gurwinder Saini; Parth Dalal; Sarosh Vandriwala; Mohammed A. Raheem; Rupesh D. Divate; Neelam L. Navlani; Vibhuti Sharma; Aashini Parikh; Siva Prasath; M. Sankar Rao; Kapil Maithal
• Keywords: 0301 basic medicine; China; COVID-19 Vaccines; SARS-CoV-2; Guinea Pigs; COVID-19; Antibodies, Viral; Antibodies, Neutralizing; Article; Rats; 3. Good health; Mice; 03 medical and health sciences; Antibody Formation; Models, Animal; Spike Glycoprotein, Coronavirus; Escherichia coli; Vaccines, DNA; Animals; Humans; Rabbits

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed intoE. colicells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500μg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels.