Abstract
BACKGROUND: We report on the safety and immunogenicity of V591, a measles vector-based SARS-CoV-2 vaccine candidate. METHODS: In this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial, healthy adults with no history of COVID-19 disease were assigned to intramuscular injection of V591 or placebo (4:1 ratio). In part 1, younger adults (18-55 years) received V591 median tissue culture infectious dose (TCID(50))-levels of 1×10(5) or 1×10(6) or placebo, 56 days apart. In part 2, younger and older (>55 years) adults received a single dose of one of four (10(4)/10(5)/10(6)/10(7)) or one of two (10(5)/10(6)) V591 TCID(50) levels, respectively, or placebo. PRIMARY OUTCOME: safety/tolerability. Secondary outcome: humoral immunogenicity. ClinicalTrials.gov: NCT04498247. FINDINGS: From August-December 2020, 444 participants were screened and 263 randomised (210 V591; 53 placebo); 262 received at least one and 10 received two doses of V591 or placebo. Adverse events were experienced by 140/209 (67.0%) V591 dose-group participants and 37/53 (69.8%) placebo-group participants following injection 1; most frequent were fatigue (57 [27.3%] vs 20 [37.7%]), headache (57 [27.3%] vs 19 [35.8%]), myalgia (35 [16.7%] vs 10 [18.9%]), and injection-site pain (35 [16.7%] vs 4 [7.5%]). No deaths nor vaccine-related serious adverse events occurred. At Day 29, no anti-SARS-CoV-2 spike serum neutralising antibody and IgG-responses were identified in placebo or the three lower V591 dose-groups; responses were detected with V591 1×10(7) TCID(50), although titres were lower than convalescent serum. INTERPRETATION: V591 was generally well tolerated, but immunogenicity was insufficient to warrant continued development. FUNDING: Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.