Safe and durable immune responses to a single dose DNA COVID-19 vaccine in previously vaccinated or SARS-CoV-2-infected adults: A phase 1 study.

An open label Phase-1 proof-of-concept study evaluated the safety and immunogenicity of IMNN-101, a DNA vaccine based on an expression plasmid and a synthetic delivery carrier (the PlaCCine vaccine), in healthy human adults previously vaccinated or infected with SARS-CoV-2. Study participants received a single intramuscular dose of 0.5 mg, 1.0 mg, or 2.0 mg of IMNN-101 DNA vaccine (n = 8 participants per group). Mild to moderate reactogenicity events were observed in 67% (16/24) of participants, including tenderness, hardening, pain, redness, swelling, and itching at the injection site, as well as fatigue, muscle aches, headache, and nausea/vomiting. Fourteen grade 1 or 2 treatment-emergent adverse events were reported: none of those attributed to IMNN-101. There were no reports of myocarditis or pericarditis. The immunization with IMNN-101 resulted in an increase in neutralizing antibody (NAb) titers against XBB.1.5 and other circulating variants of SARS-CoV-2, with 2-3-fold increase in NAb titers that were maintained during the 6-month follow up. This first-in-human evaluation of a PlaCCine-based DNA vaccine demonstrates a favorable safety profile and durable humoral immune response. The PlaCCine vaccine is thermostable, does not require a device or virus for delivery, and offers a viable alternative approach to immunization.