589. Oral Tablet Vaccination Induces Heightened Cross-Reactive CD8 T Cell Responses to SARS-COV-2 in Humans

Background Covid-19 has accelerated global demand for easily distributed vaccines. Furthermore, as variant SARS-CoV-2 strains that circumvent antibody responses emerge, cross-protective vaccines provide substantial public health benefits. Vaxart is developing a shelf stable oral tablet vaccine that incorporates both the spike (S) and the more conserved nucleocapsid (N) proteins. Vaxart’s vaccine platform uses a non-replicating adenovirus and a TLR3 agonist as an adjuvant. Methods In an open-label phase 1 clinical study, 35 healthy subjects received either a single low (1x10 10 IU; n=15) or high (5x10 10 IU; n=15) dose of the vaccine candidate VXA-CoV2-1 with a small cohort receiving 2 low doses. PBMCs were taken at pre- and 7 days post-vaccination and restimulated with S and N peptides from SARS-CoV-2 or the 4 human endemic coronaviruses (HCoV). Cells were stained for CD4/CD8/CD107a (surface) and IFNγ/TNFα (intracellular). Subjects that received an intramuscular (i.m.) mRNA vaccine had PBMCs taken at the same timepoints and were compared in the same assay. Results The study’s results indicate that the VXA-CoV2-1 tablet was well tolerated. The majority of subjects had an increase in S-specific anti-viral CD8 + T cell responses. 19/26 (73%) subjects had a measurable CD8 + T cell response on day 8 above baseline, on average 1.5-4.6%. In a comparator experiment with the 2 SARS-CoV-2 i.m. mRNA vaccines, VXA-CoV2-1 outperformed other vaccine candidates with a >3.5-fold increase in S specific antiviral CD8 T cell responses. T cell responses specific to the 4 endemic HCoV were increased by 0.6% in subjects given VXA-CoV2-1. Conclusion Here we describe a room temperature stable tablet that induces SARS-CoV-2 S specific CD8 T cells of high magnitude after one dose in humans. Overall, the level of antiviral SARS-CoV-2 specific T cells, particularly IFNg-producing CD8s, induced following oral immunization with VXA-CoV2-1 are of higher magnitude than the mRNA vaccines currently in use against COVID-19. T cell responses against 4 endemic HCoV were also induced. Because T cells may be important in protecting against death and severe infection, these results suggest that VXA-CoV2-1 could be cross-protective against a wide array of emerging pandemic coronaviruses. Disclosures Susan Johnson, PhD , Vaxart (Employee) Clarissa Martinez, MPH , Vaxart (Employee) Mario Cortese, PhD , Vaxart (Employee) Josefina Martinez, n/a , Vaxart (Employee) Shaily Garg, BS , Vaxart (Employee) Nadine Peinovich, MPH , Vaxart (Employee) Emery Dora, n/a , Vaxart (Employee) Sean Tucker, PhD , Vaxart (Employee)