A phase II/III, randomized, double-blind, placebo-controlled trial to evaluate immunogenicity and safety of the Gam-COVID-Vac combined vector vaccine in the prophylactic treatment for SARS-СoV-2 infection in the United Arab Emirates

Background: Long-term efficacy and safety profiles of the various SARS-CoV-2 vaccines were investigated. Current trial aimed to assess the safety and immunogenicity of the Gam-COVID-Vac combined vector vaccine against SARS-CoV-2-induced coronavirus infection up to 6 months post vaccination. Research design and methods: Participants ≥18 years of age with no prior SARS-COV-2 infection or vaccination were randomized on a 3:1 ratio to receive heterologous recombinant human adenovirus-vectored vaccines or placebo, respectively. Immunogenicity was determined based on quantitative IgG antibodies to viral S and N proteins, virus- neutralizing Abs (VNA), seroconversion rates, and S protein-specific CD4 and CD8 T-cell responses. Results: A total of 990 participants were randomized on a 3:1 ratio to vaccine and placebo groups. Majority of Adverse events were mild-moderate. Two doses of vaccine induced VNA in 100 % of participants on Day 42, with geometric mean ratio (GMR) peaking at 120 days with average 24.14 (p < 0.001). Vaccine group showed a very significant GMR for quantitative IgG to S protein. Seroconversion rates were 90.0 %, 83.7 % and 78.9 % on days 42, 120 and 180 (p < 0.001 compared to placebo). A significant rise in the median of S protein-specific CD4⁺ and CD8⁺ T- lymphocytes with a robust IFN-γ response was evident after 28 days compared to baseline. Long-term follow-up demonstrated persistent and significant CD8⁺ T-cell and IFN-γ responses at 120 days (p = 0.049 and 0.039, respectively) compared to placebo. Conclusions: Gam-COVID-Vac vaccine showed a good safety profile and induced durable humoral and cellular immune responses. The viral-specific CD8+ T-cell response was more durable following vaccination than CD4+ T cell counterpart. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04656613).