Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine.
Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine.
复制标题
DOI：
10.1056/nejmoa2034201
复制
发表时间：
2021-05-13
期刊：
影响因子：
--
通讯作者：
Schuitemaker H
中科院分区：
文献类型：
--
作者：
Sadoff J;Le Gars M;Shukarev G;Heerwegh D;Truyers C;de Groot AM;Stoop J;Tete S;Van Damme W;Leroux-Roels I;Berghmans PJ;Kimmel M;Van Damme P;de Hoon J;Smith W;Stephenson KE;De Rosa SC;Cohen KW;McElrath MJ;Cormier E;Scheper G;Barouch DH;Hendriks J;Struyf F;Douoguih M;Van Hoof J;Schuitemaker H
迫切需要有效的疫苗来遏制正在发生的 2019 年冠状病毒病 (Covid-19) 大流行，即严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染。候选疫苗 Ad26.COV2.S 是一种重组、无法复制的腺病毒血清型 26 (Ad26) 载体，编码全长且稳定的 SARS-CoV-2 刺突蛋白。在这项多中心、安慰剂对照、1-2a 期试验中，我们随机分配年龄在 18 至 55 岁之间的健康成年人（队列 1）和 65 岁或以上的健康成年人（队列 3）接受 Ad26.COV2.S 疫苗，剂量为每毫升 5×1010 个病毒颗粒（低剂量）或 1×1011 个病毒颗粒（高剂量），单剂或安慰剂两剂时间表。第 2 组正在收集比较单剂量方案与两剂量方案的长期数据；这里没有报告这些结果。主要终点是每个剂量方案的安全性和反应原性。第 1 组和第 3 组的 805 名参与者接种第一剂疫苗后，以及第 1 组的第二剂疫苗后，最常见的不良事件是疲劳、头痛、肌痛和注射部位疼痛。最常见的全身不良事件是发烧。第 3 组的全身不良事件比第 1 组少见，并且接受低剂量疫苗的患者比接受高剂量疫苗的患者少见。第二剂后反应原性较低。无论疫苗剂量或年龄组如何，在第一剂疫苗接种后第 29 天，90% 或更多的所有参与者检测到针对野生型病毒的中和抗体滴度（几何平均滴度 [GMT]，224 至 354），并在第 57 天达到 100%，队列 1a 中滴度进一步增加（GMT，288 至 488）。滴度至少在第 71 天之前保持稳定。第二剂使滴度增加了 2.6 至 2.9 倍（GMT，827 至 1266）。刺突结合抗体反应与中和抗体反应相似。第 14 天，队列 1 中 76% 至 83% 的参与者和队列 3 中 60% 至 67% 的参与者检测到 CD4+ T 细胞反应，其中明显偏向 1 型辅助 T 细胞。 CD8+ T 细胞反应总体强劲，但在队列 3 中较低。Ad26.COV2.S 的安全性和免疫原性特征支持该候选疫苗的进一步开发。 （由强生公司和卫生与公众服务部生物医学高级研究与开发局资助；COV1001 ClinicalTrials.gov 编号，NCT04436276。）
Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein. In this multicenter, placebo-controlled, phase 1–2a trial, we randomly assigned healthy adults between the ages of 18 and 55 years (cohort 1) and those 65 years of age or older (cohort 3) to receive the Ad26.COV2.S vaccine at a dose of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) per milliliter or placebo in a single-dose or two-dose schedule. Longer-term data comparing a single-dose regimen with a two-dose regimen are being collected in cohort 2; those results are not reported here. The primary end points were the safety and reactogenicity of each dose schedule. After the administration of the first vaccine dose in 805 participants in cohorts 1 and 3 and after the second dose in cohort 1, the most frequent solicited adverse events were fatigue, headache, myalgia, and injection-site pain. The most frequent systemic adverse event was fever. Systemic adverse events were less common in cohort 3 than in cohort 1 and in those who received the low vaccine dose than in those who received the high dose. Reactogenicity was lower after the second dose. Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 224 to 354), regardless of vaccine dose or age group, and reached 100% by day 57 with a further increase in titers (GMT, 288 to 488) in cohort 1a. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1266). Spike-binding antibody responses were similar to neutralizing-antibody responses. On day 14, CD4+ T-cell responses were detected in 76 to 83% of the participants in cohort 1 and in 60 to 67% of those in cohort 3, with a clear skewing toward type 1 helper T cells. CD8+ T-cell responses were robust overall but lower in cohort 3. The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate. (Funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.)