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.

Adolescent Adult COVID-19 / genetics COVID-19 Vaccines / administration & dosage Double-Blind Method Female Genetic Vectors Humans Immunogenicity, Vaccine Male Measles virus Middle Aged SARS-CoV-2 / genetics

COVID-19 SARS-CoV-2 measles vector vaccine

Journal

EBioMedicine

ISSN: 2352-3964

Titre abrégé: EBioMedicine

Pays: Netherlands

ID NLM: 101647039

Informations de publication

Date de publication:
Jan 2022

Historique:

received: 02 08 2021

revised: 20 12 2021

accepted: 27 12 2021

pubmed: 20 1 2022

medline: 2 2 2022

entrez: 19 1 2022

Statut: ppublish

Résumé

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 × 10 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).

Sections du résumé

BACKGROUND BACKGROUND

V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.

METHODS 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

FINDINGS RESULTS

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 CONCLUSIONS

While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development.

FUNDING BACKGROUND

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

Identifiants

DOI: 10.1016/j.ebiom.2021.103810 PMID: 35045362 PMC: PMC8761070

pubmed: 35045362

pii: S2352-3964(21)00604-6

doi: 10.1016/j.ebiom.2021.103810

pmc: PMC8761070

pii:

doi:

Substances chimiques

COVID-19 Vaccines 0

Banques de données

ClinicalTrials.gov

['NCT04497298']

Types de publication

Clinical Trial, Phase I Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

Pagination

103810

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests KR, RT, YT, AG, MM are employees of Themis Bioscience GmbH, a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. KR, RT, MM possess stock options of Merck & Co. A patent application including the design of V591 has been filed by the Institut Pasteur and is part of a licensing agreement between the Institut Pasteur and Themis/MSD, NE and CG are inventors. CIC Cochin-Pasteur, SGS, INSERM, Bioaster received payment to conduct the study. All other authors declare no conflict of interest.