Safety and immunogenicity of the measles vector-based SARS-CoV-2 vaccine candidate, V591, in adults: results from a phase 1/2 randomised, double-blind, placebo-controlled, dose-ranging trial

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.

Efficacy and safety of COVID‐19 vaccines: A network meta‐analysis

“…The other one 38 included HIV patients solely and no other trials included/provided data about HIV patients thus it was excluded. As a result, 49 trials from 48 articles 28–35,37,39–50,52–78 that included 421,173 participants and assessed 28 vaccines of 9 different types were included in the final analysis. The detailed selection process is described in Figure S1.…”

“…The other one 38 included HIV patients solely and no other trials included/provided data about HIV patients thus it was excluded. As a result, 49 trials from 48 articles 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 that included 421,173 participants and assessed 28 vaccines of 9 different types were included in the final analysis. The detailed selection process is described in Figure…”

Accelerating model-informed decisions for COVID-19 vaccine candidates using a model-based meta-analysis approach

“…This modelling was used to help inform decisions on vaccine candidates, as reported elsewhere. 45 , 46 …”

Versatility of live-attenuated measles viruses as platform technology for recombinant vaccines

“…For the vaccines targeting the coronaviruses SARS-CoV, MERS-CoV, or SARS-CoV-2, modified forms of the respective Spike proteins (S) were also tested to enhance their immunogenicity. For this purpose, genes encoding soluble S without membrane anchor 31 – 33 , or stabilized S frozen in the pre-fusion conformation by the introduction of few key mutations and deleting the protease cleavage motif separating the two subunits S1 and S2 32 , 34 – 36 were generated and tested. Stabilization of S in the pre-fusion conformation enhances the presentation of portions of the protein that are targets of nAb 32 , 37 .…”