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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.
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.
  • Launay O; Université de Paris, CIC Cochin-Pasteur; APHP, Hôpital Cochin; INSERM CIC1417, Paris, France.
  • Artaud C; Institut Pasteur, Université de Paris, Centre de Recherche Translationnelle, Paris, France.
  • Lachâtre M; Université de Paris, CIC Cochin-Pasteur; APHP, Hôpital Cochin; INSERM CIC1417, Paris, France.
  • Ait-Ahmed M; Institut Pasteur, Université de Paris, Centre de Recherche Translationnelle, Paris, France.
  • Klein J; SGS, Clinical Pharmacology Unit, Antwerpen, Belgium.
  • Luong Nguyen LB; Université de Paris, CIC Cochin-Pasteur; APHP, Hôpital Cochin; INSERM CIC1417, Paris, France.
  • Durier C; INSERM, SC10-US019, Villejuif, France.
  • Jansen B; SGS, Mechelen, Belgium.
  • Tomberger Y; Themis Bioscience GmbH, Vienna, Austria, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, United States.
  • Jolly N; Institut Pasteur, Université de Paris, Centre de Recherche Translationnelle, Paris, France.
  • Grossmann A; Themis Bioscience GmbH, Vienna, Austria, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, United States.
  • Tabbal H; Institut Pasteur, Université de Paris, CNRS UMR3569, Génétique Moléculaire des Virus à ARN, Paris, France.
  • Brunet J; Institut Pasteur, Université de Paris, Département de Santé Globale, Paris, France.
  • Gransagne M; Institut Pasteur, Université de Paris, Département de Santé Globale, Paris, France.
  • Choucha Z; Institut Pasteur, Université de Paris, Département de Santé Globale, Paris, France.
  • Batalie D; Institut Pasteur, Université de Paris, CNRS UMR3569, Génétique Moléculaire des Virus à ARN, Paris, France.
  • Delgado A; Bioaster, Lyon, France.
  • Müllner M; Themis Bioscience GmbH, Vienna, Austria, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, United States.
  • Tschismarov R; Themis Bioscience GmbH, Vienna, Austria, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, United States.
  • Berghmans PJ; SGS, Clinical Pharmacology Unit, Antwerpen, Belgium.
  • Martin A; Institut Pasteur, Université de Paris, CNRS UMR3569, Génétique Moléculaire des Virus à ARN, Paris, France.
  • Ramsauer K; Themis Bioscience GmbH, Vienna, Austria, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, United States.
  • Escriou N; Institut Pasteur, Université de Paris, Département de Santé Globale, Paris, France. Electronic address: nicolas.escriou@pasteur.fr.
  • Gerke C; Institut Pasteur, Université de Paris, Innovation Office, Vaccine Programs, Paris, France. Electronic address: christiane.gerke@pasteur.fr.
EBioMedicine ; 75: 103810, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1634471
ABSTRACT

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 × 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.

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.

FUNDING:

Themis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA; Coalition for Epidemic Preparedness Innovations (CEPI).
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunogenicity, Vaccine / COVID-19 Vaccines / Genetic Vectors / SARS-CoV-2 / COVID-19 / Measles virus Type of study: Controlled clinical trial / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Female / Humans / Male / Middle aged Language: English Journal: EBioMedicine Year: 2022 Document Type: Article Affiliation country: J.ebiom.2021.103810

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunogenicity, Vaccine / COVID-19 Vaccines / Genetic Vectors / SARS-CoV-2 / COVID-19 / Measles virus Type of study: Controlled clinical trial / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Female / Humans / Male / Middle aged Language: English Journal: EBioMedicine Year: 2022 Document Type: Article Affiliation country: J.ebiom.2021.103810