In this first-in-human study, we have demonstrated that the PIV5-vectored COVID-19 intranasal CVXGA1 vaccine is well tolerated in healthy people 12 to 53 years of age and capable of priming and boosting S-specific humoral responses, eliciting robust cell–mediated immune responses as well as local nasal IgA antibody responses. The gene discussed is CD79A; the disease is COVID-19.