| Title: |
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 |
| Authors: |
Kaufmann, Johanna K; Wyllie, Keri; Zhao, Yiwen; Tea, Lasmy; Tasker, Sybil; Yeolekar, Leena R; Dhere, Rajeev; Mueller, Steffen |
| Source: |
Open Forum Infectious Diseases ; volume 10, issue Supplement_2 ; ISSN 2328-8957 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
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 5x106 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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ofid/ofad500.2469 |
| Availability: |
https://doi.org/10.1093/ofid/ofad500.2469; https://academic.oup.com/ofid/article-pdf/10/Supplement_2/ofad500.2469/53773766/ofad500.2469.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.9A840E92 |
| Database: |
BASE |