A phase 1 clinical trial of a multi-antigen SARS-CoV DNA vaccine as a booster after dose three spike-based mRNA vaccinations.

The COVID-19 pandemic was controlled by active vaccination, but emergence of viral mutations in the receptor-binding domain (RBD) of the spike (S) protein supported the need for vaccines targeting genetically stable viral domains. We developed a unique vaccine (OC-007) combining WH1-, Alpha-, and Beta-variant RBD loops; the membrane (M; WH1); and nucleoproteins (N; WH1). In a first-in-human, placebo-controlled, randomized, double-blind, dose-escalation phase 1 clinical trial, the OC-007 DNA vaccine was evaluated as one booster dose delivered intramuscularly by in vivo electroporation (EP) in 16 healthy volunteers (HVs) who had received three mRNA vaccinations. The HVs received 0.5, 1.0, or 2.0 mg of OC-007 or placebo (NaCl) by EP and were followed for 3 months. The OC-007 vaccine was safe and tolerable with no severe adverse events. There was a 2.0- to 5.7-fold increase in antibody levels to the S Beta variant and to the N protein in the 2.0 mg dose group, in which two participants had a COVID-19 diagnosis on days 21 and 28, respectively. Neutralizing antibody levels increased to SARS-CoV-2 Beta (1.0 and 2.0 mg groups) and Omicron XBB1.5 variants (2.0 mg group). The novel OC-007 DNA vaccine was safe, tolerable, and induced/boosted T cell responses to genetically stable proteins.