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
Jonathan A. Robbins,
Dereck Tait,
Qinlei Huang,
Sheri Dubey,
Tami Crumley,
Josee Cote,
Julie Luk,
Jeffrey R. Sachs,
Kathryn Rutkowski,
Harriet Park,
Robert Schwab,
William Joseph Howitt,
Juan Carlos Rondon,
Martha Hernandez-Illas,
Terry O'Reilly,
William Smith,
Jakub Simon,
Cathy Hardalo,
Xuemei Zhao,
Richard Wnek,
Alethea Cope,
Eseng Lai,
Paula Annunziato,
Dalya Guris,
S. Aubrey Stoch
Affiliations
Jonathan A. Robbins
Merck & Co., Inc., Rahway, New Jersey, USA; Corresponding author.
Dereck Tait
The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA
Qinlei Huang
Merck & Co., Inc., Rahway, New Jersey, USA
Sheri Dubey
Merck & Co., Inc., Rahway, New Jersey, USA
Tami Crumley
Merck & Co., Inc., Rahway, New Jersey, USA
Josee Cote
Merck & Co., Inc., Rahway, New Jersey, USA
Julie Luk
Merck & Co., Inc., Rahway, New Jersey, USA
Jeffrey R. Sachs
Merck & Co., Inc., Rahway, New Jersey, USA
Kathryn Rutkowski
The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA
Harriet Park
The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA
Robert Schwab
Celerion, Lincoln, Nebraska, USA
William Joseph Howitt
Bio-Kinetic Clinical Applications (QPS), Missouri, USA
Juan Carlos Rondon
Clinical Pharmacology of Miami, Florida, USA
Martha Hernandez-Illas
QPS Miami Research Associates, Florida, USA
Terry O'Reilly
Celerion, Lincoln, Nebraska, USA
William Smith
Alliance for Multispecialty Research, LLC, Knoxville, Tennessee, USA
Jakub Simon
Merck & Co., Inc., Rahway, New Jersey, USA
Cathy Hardalo
Merck & Co., Inc., Rahway, New Jersey, USA
Xuemei Zhao
Merck & Co., Inc., Rahway, New Jersey, USA
Richard Wnek
Merck & Co., Inc., Rahway, New Jersey, USA
Alethea Cope
The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA
Summary: 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 × 105; 2.40 × 106; 1.15 × 107; or 5.55 × 107 plaque-forming units [pfu]) or placebo. In Part 3, a single V590 dose level (5.55 × 10⁷ 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 × 107 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.
