Evaluation of long-term anti-Spike immune response following a novel coronavirus vaccine (CORVax): electroporation of SARS-CoV-2 Spike plasmid DNA plus plasmid IL-12
AAI Annual Meeting; May 6-10; Portland, OR. 2022
oregon; chiles; covid-19
The global SARS-CoV-2 (CoV2) pandemic has focused efforts to generate effective vaccines that induce potent and persistent immunity. Recently, we described a novel vaccine approach using electroporation (EP) of a plasmid encoding a prefusion stabilized SARS-CoV-2 spike protein (CORVax) plus plasmid IL-12. It’s been demonstrated that IL-12 is an effective vaccine adjuvant leading to increased Th1 and Th2 antibodies in the serum. Here we examine the persistence of anti-Spike antibodies present in the serum of mice one year following vaccination. C57BL/6 and BALB/c were vaccinated via intramuscular (IM) and/or intradermal (ID) injection followed immediately by EP of plasmids encoding the SARS-CoV-2 spike protein with or without plasmid-encoded murine IL-12. Splenocytes and serum were harvested at various time points to interrogate virus-specific cellular responses as well anti-spike antibody titers. EP of CORVax was able to elicit anti-Spike IgG antibodies titers (IC50 = 1/2112), as well as EP of CORVax combined with IL-12 (IC50 = 1/4214) approximately 40 days after the booster vaccination. These anti-Spike IgG titers decayed over time but were still present 1 year after vaccination: CORVax (IC50 = 1/351 day146, IC50 = 1/208 day383); CORVax + IL12 (IC50 = 1/590 day146, IC50 = 1/266 day383). Our data shows that EP of CORVax induces IgG responses to SARS-CoV-2 Spike and the receptor binding domain. At one year following vaccination the anti-Spike IgG titers were higher in mice that received CORVax plus IL-12, however the rate at which the titers waned from their initial peak was comparable whether the mice received IL-12 or not. Additional studies are ongoing to determine whether the addition of IL-12 will enhance an anti-Spike memory response Conclusions: These data show that in vivo electroporation of CORVax induces IgG responses to SARS-CoV-2 Spike and the Spike receptor binding domain (RBD) as well as T cell responses to Spike peptides. The addition of IL-12 plasmid with CORVax resulted in elevated serum proinflammatory cytokines/chemokines 24 hours after vaccination and enhance ability to block Spike/ACE2 interactions. Spike antibody titers waned over time but were still present 1-year post vaccination. A percentage of mice (5/11) exposed to Spike protein 21 months following CORVax vaccination exhibited a recall antibody response.
Jensen, SM; Fox, Bernard A; and See full list of authors in comments, "Evaluation of long-term anti-Spike immune response following a novel coronavirus vaccine (CORVax): electroporation of SARS-CoV-2 Spike plasmid DNA plus plasmid IL-12" (2022). Articles, Abstracts, and Reports. 6125.