Intradermal administration of DNA vaccine targeting Omicron SARS-CoV-2 via pyro-drive jet injector provides the prolonged neutralizing antibody production via germinal center reaction

Abstract

Abstract Emerging SARS-CoV-2 Omicron variants are highly contagious with enhanced immune escape mechanisms against the initially approved COVID-19 vaccines. Therefore, we require stable alternative-platform vaccines that confer protection against newer variants of SARS-CoV-2. We designed an Omicron B.1.1.529 specific DNA vaccine using our DNA vaccine platform and evaluated the humoral and cellular immune responses. SD rats intradermally administered with Omicron-specific DNA vaccine via pyro-drive jet injector (PJI) thrice at 2-week intervals elicited high antibody titers against the Omicron subvariants as well as the ancestral strain. Indeed, the Omicron B.1.1.529-specific antibody titer and neutralizing antibody were higher than that of other strains. Longitudinal monitoring indicated that anti-spike (ancestral and Omicron) antibody titers decreased toward 30 weeks after the first vaccination dose. However, neutralization activity remained unaltered. Germinal center formation was histologically detected in lymph nodes in rats immunized with Omicron DNA vaccine. Ancestral spike-specific immune cell response was slightly weaker than Omicron spike-specific response in splenocytes with Omicron-adapted DNA vaccine, evaluated by ELISpot assay. Collectively, our findings suggest that Omicron targeting DNA vaccines via PJI can elicit robust durable antibody production mediated by germinal center reaction against this new variant as well as partially against the spike protein of other SARS-CoV-2 variants.