Phase 2 Evaluation of two GEO-CM04S1 Dose Levels Shows Comparable Safety and Broad Immunogenicity.

BACKGROUND: GEO-CM04S1 is a synthetic modified vaccinia Ankara (sMVA)-based SARS-CoV-2 vaccine expressing Spike (S) and Nucleocapsid (N) antigens derived from the ancestral Wuhan-Hu-1 reference strain. This phase 2 study evaluated the safety and immunogenicity of two GEO-CM04S1 dose levels administered as a single booster in healthy adults previously vaccinated against COVID-19. METHODS: In this randomized, double-blind, parallel-group trial, participants received a single intramuscular booster of GEO-CM04S1 at either 1 × 10⁷ PFU (DL1) or 1 × 10⁸ PFU (DL2). Safety was assessed through adverse events and clinical evaluations. Humoral and cellular immune responses were measured for up to one year using SARS-CoV-2-specific IgG, neutralizing antibody assays against D614G, Omicron BA.1, and XBB.1.5, cytokine secretion, and activation-induced marker (AIM) assays. RESULTS: Sixty-three participants were enrolled (31 DL1; 32 DL2). GEO-CM04S1 was well tolerated at both dose levels, with no vaccine-related serious adverse events. Both doses elicited robust binding and neutralizing antibody responses, including cross-neutralization of Omicron variants, and durable Th1-biased cellular immunity. DL2 induced modestly higher anti-S and anti-RBD binding antibody responses at selected time points, whereas neutralizing antibody and T-cell responses were comparable between dose groups. CONCLUSIONS: GEO-CM04S1 demonstrated a favourable safety profile and induced durable, broad humoral and cellular immune responses as a booster. Comparable functional immune responses between dose levels support the lower dose as a dose-sparing strategy for next-generation COVID-19 vaccination.