Safety and immunogenicity of intramuscular, single-dose V590 (rVSV-SARS-CoV-2 Vaccine) in healthy adults: Results from a phase 1 randomised, double-blind, placebo-controlled, dose-ranging trial.


Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Aug 2022
Historique:
received: 09 07 2021
revised: 01 06 2022
accepted: 17 06 2022
pubmed: 10 7 2022
medline: 17 8 2022
entrez: 9 7 2022
Statut: ppublish

Résumé

Vaccines against COVID-19 are needed to overcome challenges associated with mitigating the global pandemic. We report the safety and immunogenicity of V590, a live recombinant vesicular stomatitis virus-based COVID-19 vaccine candidate. In this placebo-controlled, double-blind, three-part phase 1 study, healthy adults were randomised to receive a single intramuscular dose of vaccine or placebo. In Part 1, younger (18-54 years) and, in Part 2, older (≥55 years) adults seronegative for SARS-CoV-2 nucleocapsid received one of four V590 dose levels (5.00 × 10 232 participants were randomised and 219 completed the study. In seronegative participants, anti-SARS-CoV-2 spike-specific antibody responses to V590 were low and comparable to placebo across the lower dose levels. At the highest dose level (5.55 × 10 V590 was generally well-tolerated. However, Day 28 anti-SARS-Cov-2 spike-specific antibody responses in seronegative participants following a single intramuscular administration of V590 were not sufficient to warrant continued development. The study was funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Sections du résumé

BACKGROUND BACKGROUND
Vaccines against COVID-19 are needed to overcome challenges associated with mitigating the global pandemic. We report the safety and immunogenicity of V590, a live recombinant vesicular stomatitis virus-based COVID-19 vaccine candidate.
METHODS METHODS
In this placebo-controlled, double-blind, three-part phase 1 study, healthy adults were randomised to receive a single intramuscular dose of vaccine or placebo. In Part 1, younger (18-54 years) and, in Part 2, older (≥55 years) adults seronegative for SARS-CoV-2 nucleocapsid received one of four V590 dose levels (5.00 × 10
FINDINGS RESULTS
232 participants were randomised and 219 completed the study. In seronegative participants, anti-SARS-CoV-2 spike-specific antibody responses to V590 were low and comparable to placebo across the lower dose levels. At the highest dose level (5.55 × 10
INTERPRETATION CONCLUSIONS
V590 was generally well-tolerated. However, Day 28 anti-SARS-Cov-2 spike-specific antibody responses in seronegative participants following a single intramuscular administration of V590 were not sufficient to warrant continued development.
FUNDING BACKGROUND
The study was funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Identifiants

pubmed: 35809371
pii: S2352-3964(22)00319-X
doi: 10.1016/j.ebiom.2022.104138
pmc: PMC9259069
pii:
doi:

Substances chimiques

Antibodies, Viral 0
COVID-19 Vaccines 0
Vaccines 0

Banques de données

ClinicalTrials.gov
['NCT04569786']

Types de publication

Clinical Trial, Phase I Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

104138

Informations de copyright

Copyright © 2022 Merck Sharp & Dohme Corp., a subsidiary Merck & Co., Inc., The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests JAR, QH, SD, TC, JC, JL, JS, CH, XZ, RW, EL, PA, DG and SAS are employees of Merck Sharpe & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. JRS is an employee of Merck Sharpe & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA holding stocks alongside stocks in various pharmaceutical and biotechnology companies and service providers, has participated on various editorial boards and committees for Society for Industrial and Applied Mathematics and is a member and participant in committees for the International Society of Pharmacometrics. All other authors report no conflicts of interest.

Auteurs

Jonathan A Robbins (JA)

Merck & Co., Inc., Rahway, New Jersey, USA. Electronic address: jonathan.robbins@merck.com.

Dereck Tait (D)

The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.

Qinlei Huang (Q)

Merck & Co., Inc., Rahway, New Jersey, USA.

Sheri Dubey (S)

Merck & Co., Inc., Rahway, New Jersey, USA.

Tami Crumley (T)

Merck & Co., Inc., Rahway, New Jersey, USA.

Josee Cote (J)

Merck & Co., Inc., Rahway, New Jersey, USA.

Julie Luk (J)

Merck & Co., Inc., Rahway, New Jersey, USA.

Jeffrey R Sachs (JR)

Merck & Co., Inc., Rahway, New Jersey, USA.

Kathryn Rutkowski (K)

The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.

Harriet Park (H)

The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.

Robert Schwab (R)

Celerion, Lincoln, Nebraska, USA.

William Joseph Howitt (WJ)

Bio-Kinetic Clinical Applications (QPS), Missouri, USA.

Juan Carlos Rondon (JC)

Clinical Pharmacology of Miami, Florida, USA.

Martha Hernandez-Illas (M)

QPS Miami Research Associates, Florida, USA.

Terry O'Reilly (T)

Celerion, Lincoln, Nebraska, USA.

William Smith (W)

Alliance for Multispecialty Research, LLC, Knoxville, Tennessee, USA.

Jakub Simon (J)

Merck & Co., Inc., Rahway, New Jersey, USA.

Cathy Hardalo (C)

Merck & Co., Inc., Rahway, New Jersey, USA.

Xuemei Zhao (X)

Merck & Co., Inc., Rahway, New Jersey, USA.

Richard Wnek (R)

Merck & Co., Inc., Rahway, New Jersey, USA.

Alethea Cope (A)

The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.

Eseng Lai (E)

Merck & Co., Inc., Rahway, New Jersey, USA.

Paula Annunziato (P)

Merck & Co., Inc., Rahway, New Jersey, USA.

Dalya Guris (D)

Merck & Co., Inc., Rahway, New Jersey, USA.

S Aubrey Stoch (SA)

Merck & Co., Inc., Rahway, New Jersey, USA.

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Classifications MeSH