Intradermal-delivered DNA vaccine induces durable immunity mediating a reduction in viral load in a rhesus macaque SARS-CoV-2 challenge model

Patel, Ami; Walters, Jewell N.; Reuschel, Emma L.; Schultheis, Katherine; Parzych, Elizabeth; Gary, Ebony N.; Maricic, Igor; Purwar, Mansi; Eblimit, Zeena; Walker, Susanne N.; Guimet, Diana; Bhojnagarwala, Pratik; Adeniji, Opeyemi S.; Doan, Arthur; Xu, Ziyang; Elwood, Dustin; Reeder, Sophia M.; Pessaint, Laurent; Kim, Kevin Y.; Cook, Anthony; Chokkalingam, Neethu; Finneyfrock, Brad; Tello-Ruiz, Edgar; Dodson, Alan; Choi, Jihae; Generotti, Alison; Harrison, John; Tursi, Nicholas J.; Andrade, Viviane M.; Dia, Yaya; Zaidi, Faraz I.; Andersen, Hanne; Abdel-Mohsen, Mohamed; Lewis, Mark G.; Muthumani, Kar; Kim, J Joseph; Kulp, Daniel W.; Humeau, Laurent M.; Ramos, Stephanie J.; Smith, Trevor R.F.; Weiner, David B.; Broderick, Kate E.

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease.