Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study
Résumé
Background V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.
Methods We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a dou- ble-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each compris- ing 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 £ 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 £ 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immuno- genicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298.
Findings Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment- related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiv- ing the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine.
Interpretation While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.
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Launay-2022_V591 clinical trial.pdf (1.16 Mo)
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Launay-2022_V591 clinical trial_Supplementary Figure_CD4 and CD8 T cell responses.pdf (432.33 Ko)
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Launay-2022_V591 clinical trial_Supplementary data-Study Protocol.pdf (1.66 Mo)
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