PMID- 35809371
OWN - NLM
STAT- MEDLINE
DCOM- 20220816
LR  - 20220818
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 82
DP  - 2022 Aug
TI  - 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.
PG  - 104138
LID - S2352-3964(22)00319-X [pii]
LID - 10.1016/j.ebiom.2022.104138 [doi]
LID - 104138
AB  - 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: 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 x 10(5); 2.40 x 10(6); 1.15 x 10(7); 
      or 5.55 x 10(7) plaque-forming units [pfu]) or placebo. In Part 3, a single V590 
      dose level (5.55 x 10(7) pfu) or placebo was administered to younger SARS-CoV-2 
      seropositive adults. Primary endpoints included adverse events (AEs) and for 
      Parts 1 and 2 anti-SARS-CoV-2 serum neutralising antibody responses measured by 
      50% plaque reduction neutralisation (PRNT50) assay at Day 28. Registration 
      NCT04569786 [P001-02]. FINDINGS: 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 x 10(7) pfu), anti-SARS-CoV-2 
      spike-specific PRNT50 was 2.3-fold higher than placebo. The most frequently 
      reported AEs were injection-site pain (38.4%), headache (15.1%) and fatigue 
      (13.4%). INTERPRETATION: 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: The study was funded by Merck Sharp & 
      Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
CI  - Copyright (c) 2022 Merck Sharp & Dohme Corp., a subsidiary Merck & Co., Inc., The 
      Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Robbins, Jonathan A
AU  - Robbins JA
AD  - Merck & Co., Inc., Rahway, New Jersey, USA. Electronic address: 
      jonathan.robbins@merck.com.
FAU - Tait, Dereck
AU  - Tait D
AD  - The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.
FAU - Huang, Qinlei
AU  - Huang Q
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Dubey, Sheri
AU  - Dubey S
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Crumley, Tami
AU  - Crumley T
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Cote, Josee
AU  - Cote J
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Luk, Julie
AU  - Luk J
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Sachs, Jeffrey R
AU  - Sachs JR
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Rutkowski, Kathryn
AU  - Rutkowski K
AD  - The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.
FAU - Park, Harriet
AU  - Park H
AD  - The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.
FAU - Schwab, Robert
AU  - Schwab R
AD  - Celerion, Lincoln, Nebraska, USA.
FAU - Howitt, William Joseph
AU  - Howitt WJ
AD  - Bio-Kinetic Clinical Applications (QPS), Missouri, USA.
FAU - Rondon, Juan Carlos
AU  - Rondon JC
AD  - Clinical Pharmacology of Miami, Florida, USA.
FAU - Hernandez-Illas, Martha
AU  - Hernandez-Illas M
AD  - QPS Miami Research Associates, Florida, USA.
FAU - O'Reilly, Terry
AU  - O'Reilly T
AD  - Celerion, Lincoln, Nebraska, USA.
FAU - Smith, William
AU  - Smith W
AD  - Alliance for Multispecialty Research, LLC, Knoxville, Tennessee, USA.
FAU - Simon, Jakub
AU  - Simon J
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Hardalo, Cathy
AU  - Hardalo C
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Zhao, Xuemei
AU  - Zhao X
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Wnek, Richard
AU  - Wnek R
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Cope, Alethea
AU  - Cope A
AD  - The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.
FAU - Lai, Eseng
AU  - Lai E
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Annunziato, Paula
AU  - Annunziato P
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Guris, Dalya
AU  - Guris D
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
FAU - Stoch, S Aubrey
AU  - Stoch SA
AD  - Merck & Co., Inc., Rahway, New Jersey, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT04569786
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220706
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (Antibodies, Viral)
RN  - 0 (COVID-19 Vaccines)
RN  - 0 (Vaccines)
SB  - IM
MH  - Adult
MH  - Antibodies, Viral
MH  - *COVID-19/prevention & control
MH  - *COVID-19 Vaccines/adverse effects
MH  - Double-Blind Method
MH  - Humans
MH  - Pandemics/prevention & control
MH  - SARS-CoV-2
MH  - Vaccines
PMC - PMC9259069
OTO - NOTNLM
OT  - COVID-19
OT  - SARS-CoV-2
OT  - V590
OT  - Vaccine
OT  - Vesicular stomatitis virus (VSV)
COIS- 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.
EDAT- 2022/07/10 06:00
MHDA- 2022/08/17 06:00
PMCR- 2022/07/06
CRDT- 2022/07/09 18:14
PHST- 2021/07/09 00:00 [received]
PHST- 2022/06/01 00:00 [revised]
PHST- 2022/06/17 00:00 [accepted]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/08/17 06:00 [medline]
PHST- 2022/07/09 18:14 [entrez]
PHST- 2022/07/06 00:00 [pmc-release]
AID - S2352-3964(22)00319-X [pii]
AID - 104138 [pii]
AID - 10.1016/j.ebiom.2022.104138 [doi]
PST - ppublish
SO  - EBioMedicine. 2022 Aug;82:104138. doi: 10.1016/j.ebiom.2022.104138. Epub 2022 Jul 
      6.