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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

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 double-blind treatment phase at 2 sites in...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761070/
https://www.ncbi.nlm.nih.gov/pubmed/35045362
http://dx.doi.org/10.1016/j.ebiom.2021.103810
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author 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
author_facet 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
author_sort Launay, Odile
collection PubMed
description 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 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 × 10(5) median Tissue Culture Infectious Dose [TCID(50)]), one or two injections of a high dose vaccine (1 × 10(6) TCID(50)), 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. 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 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. INTERPRETATION: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.
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spelling pubmed-87610702022-01-18 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 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 EBioMedicine Articles 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 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 × 10(5) median Tissue Culture Infectious Dose [TCID(50)]), one or two injections of a high dose vaccine (1 × 10(6) TCID(50)), 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. 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 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. INTERPRETATION: While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development. Elsevier 2022-01-16 /pmc/articles/PMC8761070/ /pubmed/35045362 http://dx.doi.org/10.1016/j.ebiom.2021.103810 Text en © 2022 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA, The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761070/
https://www.ncbi.nlm.nih.gov/pubmed/35045362
http://dx.doi.org/10.1016/j.ebiom.2021.103810
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