Safety and immunogenicity of intranasal parainfluenza virus type 5 (PIV5)-vectored COVID-19 vaccine in adults and teens in an open-label phase 1 trial.

COVID-19 continues causing substantial mortality despite existing FDA-approved COVID-19 vaccines. An effective COVID-19 vaccine providing durable immunity with minimal reactogenicity is needed. CVXGA1, a PIV5-based intranasal COVID-19 vaccine expressing the Spike (S) protein of SARS-CoV-2, was evaluated in this phase 1 study in adults and teens. CVXGA1 was well tolerated without serious adverse events (AEs) or fever reported. Solicited local and systemic AEs were mostly mild. CVXGA1 elicited S-specific serum and mucosal antibodies and CD8+ cytotoxic T lymphocyte responses in all groups. Significantly lower rates of symptomatic COVID-19 infection were reported in groups receiving high-dose CVXGA1 (HD) compared to that in the group receiving low-dose CVXGA1 (LD) during the SARS-CoV-2 delta and omicron waves. The data indicate that CVXGA1 is a potentially effective intranasal COVID-19 vaccine that is immunogenic with minimal reactogenicity.