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

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; V590; Vaccine; Vesicular stomatitis virus (VSV).

Conflict of interest statement

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.

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

Figures

Figure 1

Schematic of the VSV SARS-CoV-2 construct (a) and a cryo transmission electron microscopy image of V590 GMP bulk drug substance (image courtesy of Irene Yin-Ting Chang and Douglas D. Richardson) (b).

Figure 2

Study design.

Figure 3

Participant disposition.

Figure 4

Incidence and severity of adverse events after injection of V590 or placebo. Adverse events with an incidence of 5% or higher reported up to 28 days after injection. Each panel presents a specific adverse event. Data are grouped by treatment group.

Figure 5

Analysis of anti-SARS-CoV-2 spike-specific antibody responses at Day 28 (per-protocol immunogenicity population) ([a] Parts 1 and 2: seronegative participants) and compared with Day 1 for seropositive participants in Part 3 ([b] 18–54 years).