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

• Published in: EBioMedicine Vol. 75; p. 103810
• Main Authors: Launay, Odile, Artaud, Cécile, Lachâtre, Marie, Ait-Ahmed, Mohand, Klein, Jelle, Luong Nguyen, Liem Binh, Durier, Christine, Jansen, Bastiaan, Tomberger, Yvonne, Jolly, Nathalie, Grossmann, Anna, Tabbal, Houda, Brunet, Jérémy, Gransagne, Marion, Choucha, Zaineb, Batalie, Damien, Delgado, Ana, Müllner, Matthias, Tschismarov, Roland, Berghmans, Pieter-Jan, Martin, Annette, Ramsauer, Katrin, Escriou, Nicolas, Gerke, Christiane
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2022; Elsevier
• Subjects: Adolescent; Adult; Biotechnology; COVID-19; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - genetics; COVID-19 Vaccines - immunology; Double-Blind Method; Female; Genetic Vectors; Human health and pathology; Humans; Immunogenicity, Vaccine; Immunology; Infectious diseases; Life Sciences; Male; measles vector; Measles virus; Middle Aged; Santé publique et épidémiologie; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; vaccine; Vaccinology; COVID-19; SARS-CoV-2; vaccine; measles vector
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2021.103810

V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein. We 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. 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 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. While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development. Themis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA; Coalition for Epidemic Preparedness Innovations (CEPI).