The following is a summary of “Safety, immunogenicity, and optimal dosing of a modified vaccinia Ankara-based vaccine against MERS-CoV in healthy adults: a phase 1b, double-blind, randomised placebo-controlled clinical trial,” published in the October 2024 issue of Infectious Disease by Raadsen et al.
MERS-CoV is a deadly respiratory virus with a 36% fatality rate with no approved vaccines. MVA-MERS-S is a potential vaccine using recombinant modified vaccinia virus Ankara (MVA).
Researchers conducted a retrospective study to assess the safety, immunogenicity, and optimal dosing of MVA-MERS-S in individuals with prior SARS-CoV-2 exposure and vaccination.
They performed a randomized controlled trial at 2 universities in Germany and the Netherlands. Healthy adults (18-55 years) were randomly assigned to receive 3 doses of either 107 or 108 plaque-forming units (PFU) of the MVA-MERS-S vaccine at 28-day or 56-day intervals between the first 2 doses. A control group received a placebo at a ratio of 2:2:2:2:1. The 3rd dose was given after 224 days. Neither participants nor researchers knew the dose or dosing interval (masked study). Safety (primary outcome) was assessed through daily solicited reactions (7 days post-dose), unsolicited events (28 days), and serious adverse events throughout the study. Immunogenicity (secondary outcome) was measured by antibody levels and seroconversion rates (all participants receiving 3 doses).
The results showed from 244 volunteers, 177 were eligible, and 140 were randomly assigned to 5 groups (28-day 107PFU [n=32], 56-day 107 PFU [n=31], 28-day 108 PFU [n=31], 56-day 108 PFU (n=30), placebo [n=16]), 178 doses of 107 PFU, 174 of 108 PFU, and 164 doses of placebo were administered. At the same time, 139 participants received at least 1 injection. There were 73 (53%) females and 66 (48%) males with no serious adverse events. Solicited local reactions were mild in 288 (93%, 95% CI 90–96) of 309 reports. Pain or tenderness occurred after 69 (39%, 32–46) of 178 107 PFU injections, 138 (79%; 73–85) of 174 108 PFU injections, and 18 (11%; 7–11) of 164 placebo injections, whereas 595 reported solicited systemic reactions, 479 (81%, 77–83) were mild. Systemic reactions occurred after 77 (43%; 36–51) 107 PFU injections, 102 (59%; 51–66) 108 PFU injections, and 67 (41%; 34–49) of 164 placebo injections. At 28 days after the 2nd dose, MERS-CoV neutralizing antibodies were highest for participants assigned to the 56-day 108 PFU group, with geometric mean ratios of 7·2 (95% CI 3·9–13·3) for the 56-day 108 PFU group vs the 28-day 108 PFU group (P <0·0001), 3·9 (2·1–7·2) for the 56-day 108 PFU group vs the 56-day 107 PFU group (P = 0·0031), and 5·4 (2·9–10·0) for the 56-day 108 PFU group vs the 28-day 107 PFU group (P = 0·0003).
They concluded that MVA-MERS-S was safe and immunogenic in individuals with SARS-CoV-2 exposure, with a stronger immune response observed with a 56-day dosing interval.
Source: thelancet.com/journals/laninf/article/PIIS1473-3099(24)00423-7/abstract
