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
Odile Launay, Cécile Artaud, Marie Lachâtre, Mohand Ait‐Ahmed, Jelle Klein, Liêm Binh Luong Nguyen, Christine Durier, Bas Jansen, Yvonne Tomberger, Nathalie Jolly, Anna Grossmann, Houda Tabbal, Jérémy Brunet, Marion Gransagne, Zaineb Choucha, Damien Batalie, Ana Sofia Delgado, Matthias Müllner, Roland Tschismarov, Pieter-Jan Berghmans, Annette Martin, Katrin Ramsauer, Nicolas Escriou, Christiane Gerke
Abstract
BackgroundV591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.MethodsWe performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-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 comprising 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. Immunogenicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298.FindingsBetween 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 receiving 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.InterpretationWhile V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.FundingThemis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA; Coalition for Epidemic Preparedness Innovations (CEPI).