Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Souseikai Hakata Clinic, Random Square 5F, 6-18, Tenyamachi, Hakata-ku, Fukuoka 812-0025, Japan.
Vaccine. 2023 Aug 31;41(38):5525-5534. doi: 10.1016/j.vaccine.2023.07.012. Epub 2023 Aug 14.
DS-5670a is a vaccine candidate for coronavirus disease 2019 (COVID-19) harnessing a novel modality composed of messenger ribonucleic acid (mRNA) encoding the receptor-binding domain (RBD) from the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encapsulated in lipid nanoparticles. Here, we report the safety, immunogenicity, and pharmacokinetic profile of DS-5670a from a phase 2 clinical trial in healthy adults who were immunologically naïve to SARS-CoV-2.
The study consisted of an open-label, uncontrolled, dose-escalation part and a double-blind, randomized, uncontrolled, 2-arm, parallel-group part. A total of 80 Japanese participants were assigned to receive intramuscular DS-5670a, containing either 30 or 60 µg of mRNA, as two injections administered 4 weeks apart. Safety was assessed by characterization of treatment-emergent adverse events (TEAEs). Immunogenicity was assessed by neutralization titers against SARS-CoV-2, anti-RBD immunoglobulin (Ig)G levels, and SARS-CoV-2 spike-specific T cell responses. Plasma pharmacokinetic parameters of DS-5670a were also evaluated.
Most solicited TEAEs were mild or moderate with both the 30 and 60 µg mRNA doses. Four participants (10 %) in the 60 µg mRNA group developed severe redness at the injection site, but all cases resolved without treatment. There were no serious TEAEs and no TEAEs leading to discontinuation. Humoral immune responses in both dose groups were greater than those observed in human convalescent serum; the 60 µg mRNA dose produced better responses. Neutralization titers were found to be correlated with anti-RBD IgG levels (specifically IgG1). DS-5670a elicited antigen-specific T helper 1-polarized cellular immune responses.
The novel mRNA-based vaccine candidate DS-5670a provided favorable immune responses against SARS-CoV-2 with a clinically acceptable safety profile. Confirmatory trials are currently ongoing to evaluate the safety and immunogenicity of DS-5670a as the primary vaccine and to assess the immunogenicity when administered as a heterologous or homologous booster.
DS-5670a 是一种针对 2019 年冠状病毒病（COVID-19）的候选疫苗，利用了一种新型模式，该模式由信使核糖核酸（mRNA）组成，编码严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白的受体结合域（RBD），该蛋白被封装在脂质纳米颗粒中。在这里，我们报告了在对 SARS-CoV-2 无免疫的健康成年人中进行的 2 期临床试验中，DS-5670a 的安全性、免疫原性和药代动力学特征。
该研究由一项开放标签、非对照、剂量递增部分和一项双盲、随机、非对照、2 臂、平行组部分组成。共有 80 名日本参与者被分配接受肌内注射 DS-5670a，剂量分别为 30 或 60µg，每 4 周注射两次。通过描述治疗后出现的不良事件（TEAE）来评估安全性。通过 SARS-CoV-2 的中和滴度、抗 RBD 免疫球蛋白（IgG）水平和 SARS-CoV-2 刺突特异性 T 细胞反应来评估免疫原性。还评估了 DS-5670a 的血浆药代动力学参数。
两种剂量的 30 和 60µg mRNA 组的大多数预期 TEAEs 均为轻度或中度。60µg mRNA 组的 4 名参与者（10%）出现注射部位严重发红，但所有病例均无需治疗即可缓解。没有严重的 TEAEs，也没有 TEAEs 导致停药。两种剂量组的体液免疫反应均大于人类恢复期血清中的反应；60µg mRNA 剂量产生了更好的反应。中和滴度与抗 RBD IgG 水平（特别是 IgG1）相关。DS-5670a 引发了针对 SARS-CoV-2 的抗原特异性辅助性 T 细胞 1 极化的细胞免疫反应。
新型基于 mRNA 的候选疫苗 DS-5670a 提供了针对 SARS-CoV-2 的有利免疫反应，具有临床可接受的安全性。目前正在进行确证性试验，以评估 DS-5670a 作为主要疫苗的安全性和免疫原性，并评估作为异源或同源加强针接种时的免疫原性。
