Merck & Co., Inc., Rahway, New Jersey, USA.
The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA.
EBioMedicine. 2022 Aug;82:104138. doi: 10.1016/j.ebiom.2022.104138. Epub 2022 Jul 6.
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; 2.40 × 10; 1.15 × 10; or 5.55 × 10 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].
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 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%).
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.
需要针对 COVID-19 的疫苗来克服减轻全球大流行的相关挑战。我们报告了 V590（一种基于水疱性口炎病毒的 COVID-19 候选疫苗）的安全性和免疫原性。
在这项安慰剂对照、双盲、三部分的 1 期研究中，健康成年人被随机分配接受单次肌内注射疫苗或安慰剂。在第 1 部分中，年轻（18-54 岁）且在第 2 部分中，年长（≥55 岁）的 SARS-CoV-2 核衣壳血清阴性者接受了四种 V590 剂量水平（5.00×10 ；2.40×10 ；1.15×10 ；或 5.55×10 噬菌斑形成单位 [pfu]）或安慰剂。在第 3 部分中，年轻的 SARS-CoV-2 血清阳性成年人接受了单次 V590 剂量水平（5.55×10 ⁷ pfu）或安慰剂。主要终点包括不良事件（AE）以及第 1 和第 2 部分在第 28 天通过 50%噬斑减少中和（PRNT50）测定法测量的抗 SARS-CoV-2 血清中和抗体反应。注册 NCT04569786 [P001-02]。
232 名参与者被随机分组，219 名完成了研究。在血清阴性参与者中，V590 对 SARS-CoV-2 刺突特异性抗体反应较低，与安慰剂在较低剂量水平相当。在最高剂量水平（5.55×10 pfu）下，抗 SARS-CoV-2 刺突特异性 PRNT50 比安慰剂高 2.3 倍。报告最频繁的不良事件是注射部位疼痛（38.4%）、头痛（15.1%）和疲劳（13.4%）。
V590 通常具有良好的耐受性。然而，在单次肌内给药后，血清阴性参与者在第 28 天针对 SARS-CoV-2 刺突的特异性抗体反应不足以证明继续开发。
该研究由默克公司的子公司默克夏普 & 多姆公司（Merck Sharp & Dohme LLC.）资助，默克公司是一家总部位于新泽西州 Rahway 的美国公司。
