One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model

• Published in: Vaccine 2021-08, Vol.39 (34), p.4885-4894
• Main Authors: Gooch, Karen E., Smith, Trevor R.F., Salguero, Francisco J., Fotheringham, Susan A., Watson, Robert J., Dennis, Mike J., Handley, Alastair, Humphries, Holly E., Longet, Stephanie, Tipton, Tom, Sarfas, Charlotte, Sibley, Laura, Slack, Gillian S., Rayner, Emma, Ryan, Kathryn A., Schultheis, Katherine, Ramos, Stephanie J., White, Andrew, Charlton, Sue, Sharpe, Sally A., Gleeson, Fergus, Humeau, Laurent M., Hall, Yper, Broderick, Kate E., Carroll, Miles W.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antigens; Coronaviruses; COVID-19; COVID-19 Vaccines; Deoxyribonucleic acid; DNA; DNA vaccine; DNA vaccines; Evaluation; Humans; Immunization; Immunogenicity; Infections; Lung diseases; Lungs; Lymphocytes; Lymphocytes T; Macaca mulatta; Nonhuman Primate Virus Challenge; Pandemics; Proteins; Respiratory tract; Respiratory tract diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Spike protein; Trachea; Vaccines; Vaccines, DNA; Viral diseases; Viral infections; Viral Vaccines; γ-Interferon
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2021.06.057

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 106 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.