1938. CoviLiv™, a Novel Intranasal Live-Attenuated COVID-19 Vaccine Candidate, Induces Robust Humoral and Cellular Immunity in First-In-Human Clinical Trial CDX-CoV-001

BACKGROUND: CoviLiv is a novel intranasal live-attenuated COVID-19 vaccine candidate, derived from SARS-CoV-2/Wuhan that was synthetically engineered utilizing Codagenix’ codon pair deoptimization platform. CDX-CoV-001 was a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults, that established its safety and tolerability (NCT04619628). Here, we characterize the immune response to CoviLiv in participants in the high-dose cohort of 5x10(6) pfu (n=6/group). METHODS: Humoral immune responses were characterized in sera (days 1, 29 and 57) with a spike-specific IgG ELISA and both microneutralization (MNT) and pseudovirus neutralization (PVN) assays. T cell functionality was analyzed in PBMCs (days 1 and 36) using interferon-γ (IFNγ) ELISpot and intracellular cytokine staining (ICS) after restimulation with peptide pools for SNMO or spike, as well as T cell receptor (TCR) sequencing combined with in silico mapping to TCRs with known antigen specificity. RESULTS: After 2 doses of CoviLiv, all participants exceeded a 2-fold increase in spike-specific IgG with a geometric mean fold rise of 19.5 (95% CI 3.4-113.8) on day 57. Neutralizing antibodies at this timepoint were induced 2.6-fold (CI 1.0-7.0) and 4.9-fold (CI 1.4-16.6) using MNT and PVN. On day 36 post-vaccination, IFNγ response by ELISpot after restimulation with the SNMO peptide pool increased 4.5-fold (CI 2.8-7.4) in the 2-dose cohort and 2.5-fold (CI 1.4-4.2) in the 1-dose cohort. No increase in IFNγ response was observed after placebo vaccination or in any group after restimulation with spike-only peptides. ICS confirmed significant regimen-dependent SNMO-specific increases in IFNγ, IL-2 and TNFα response especially in the CD4(+) T cell subset, including induction of polyfunctional CD4(+) T cells. TCR repertoire mapping revealed increases in both depth and breadth of CD4(+) T cell clones specific for spike, nucleocapsid phosphoprotein and membrane glycoprotein. CD8(+) T cell responses were less pronounced with CoviLiv-induced responses directed against nucleocapsid and ORF1ab. CONCLUSION: Two doses of CoviLiv induced a poly-antigenic immune response with specificity to targets beyond spike, including highly conserved viral proteins, highlighting the value of this differentiated vaccine candidate. DISCLOSURES: Johanna K. Kaufmann, PhD, Codagenix Inc.: Salaried employee|Codagenix Inc.: Ownership Interest Keri Wyllie, MPA, Codagenix Inc.: Salaried employee|Codagenix Inc.: Ownership Interest Yiwen Zhao, PhD, Codagenix Inc.: Salaried employee Lasmy Tea, MS, MPH, Codagenix Inc.: Salaried employee|Codagenix Inc.: Ownership Interest Sybil Tasker, MD, MPH, FIDSA, Codagenix Inc.: Advisor/Consultant|Codagenix Inc.: Salaried employee|Codagenix Inc.: Ownership Interest|Inventprise: Salaried employee|Inventprise: Ownership Interest Leena R. Yeolekar, PhD, Serum Institute of India Pvt. Ltd.: Salaried employee Rajeev Dhere, PhD, Serum Institute of India Pvt. Ltd.: Salaried employee Steffen Mueller, PhD, Codagenix Inc.: Board Member|Codagenix Inc.: Patent owner|Codagenix Inc.: Salaried employee|Codagenix Inc.: Ownership Interest