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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

Paul Spearman, Hong Jin, Peng Xiao, Kristeene A. Knopp, Henry Radziewicz, Marinka C. Tellier, Sasha E. Larsen, Bryan J. Berube, Xiao Song, J. G. Kidd, Karnail Singh, Li Zhuo, María Cristina Gingerich, Samuel Wu, Susan P. John, Angela R Branche, Ann R. Falsey, Rhea N. Coler, François Villinger, Biao He

2025Science Advances11 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

ReactogenicityImmunogenicityMedicineNasal administrationAdverse effectVirologyCoronavirus disease 2019 (COVID-19)CD8ImmunologyAntibodyInternal medicineImmune systemDiseaseInfectious disease (medical specialty)SARS-CoV-2 and COVID-19 ResearchRespiratory viral infections researchBacterial Infections and Vaccines
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 | Litcius