Prevention of incident SARS-CoV-2 infection through combined intranasal and intradermal administration of the GLS-5310 DNA vaccine during the Omicron outbreak

We evaluated the safety and immunogenicity of boost vaccination with the GLS-5310 SARS-CoV-2 DNA vaccine to those previously vaccinated with the Ad26.S.CoV2, BNT162b2, or mRNA-1273 vaccines. GLS-5310 was administered intradermally (ID) and followed by application of suction using the GeneDerm device, or ID as well as intranasally (IN) by nasal atomizer. GLS-5310 vaccination was well tolerated. With respect to primary vaccine type, boost vaccination induced a 1.5- to 4-fold increase in antibody titers, up to a 14.4-fold increase in T cell responses by ELISpot. Incident SARS-CoV-2 infections, during a period of Omicron prevalence, were reported for 24.2% of participants: 1 of 17 (5.9%) vaccinated ID plus IN versus 16 of 53 (30.2%) vaccinated ID only, p = 0.042 (chi-square analysis). This first ever trial of a DNA vaccine administered IN plus ID showed potential protection against incident SARS-CoV-2 Omicron infection. NCT Clinical Trial number: NCT05182567