From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, M.L.G., G. Shukarev, A.M.G., J. Stoop, S.T., E.C., G. Scheper, J. Hendriks, M.D., J.V.H., H.S.); Janssen Research and Development, Beerse (D.H., C.T., F.S.), Janssen Clinical Pharmacology Unit, Merksem (W.V.D.), the Center for Vaccinology, Ghent University, Gent (I.L.-R.), SGS Life Sciences (P.-J.B.) and the Center for the Evaluation of Vaccination, University of Antwerp (P.V.D.), Antwerp, and the Center for Clinical Pharmacology, University Hospitals Leuven, Leuven (J. de Hoon) - all in Belgium; Optimal Research, Melbourne, FL (M.K.); the Alliance for Multispecialty Research, Knoxville, TN (W.S.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (K.E.S., D.H.B.); and the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (S.C.D.R., K.W.C., M.J.M.).
N Engl J Med. 2021 May 13;384(19):1824-1835. doi: 10.1056/NEJMoa2034201. Epub 2021 Jan 13.
BACKGROUND: 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. METHODS: 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 5×10 viral particles (low dose) or 1×10 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. RESULTS: 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], 212 to 354), regardless of vaccine dose or age group, and reached 96% 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 15, 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. CONCLUSIONS: 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.).
背景：急需有效的疫苗来控制由严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2）引起的当前 2019 年冠状病毒病（Covid-19）大流行。候选疫苗 Ad26.COV2.S 是一种重组、复制缺陷型腺病毒血清型 26（Ad26）载体，编码全长且稳定的 SARS-CoV-2 刺突蛋白。
方法：在这项多中心、安慰剂对照、1 期-2a 试验中，我们将年龄在 18 至 55 岁之间的健康成年人（队列 1）和 65 岁及以上的成年人（队列 3）随机分配，以单剂量或双剂量方案接受每毫升 5×10 病毒颗粒（低剂量）或 1×10 病毒颗粒（高剂量）的 Ad26.COV2.S 疫苗，或安慰剂。在队列 2 中正在收集比较单剂量方案与双剂量方案的更长期数据；此处未报告这些结果。主要终点是每种剂量方案的安全性和反应原性。
结果：在队列 1 和 3 的 805 名参与者中接受第一剂疫苗后，以及在队列 1 中接受第二剂疫苗后，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热。与队列 1 相比，队列 3 的全身不良事件较少，与高剂量相比，低剂量疫苗的全身不良事件较少。第二剂后的反应原性较低。第一剂疫苗后 29 天，所有参与者的针对野生型病毒的中和抗体滴度均达到 90%或更高（几何平均滴度[GMT]，212 至 354），无论疫苗剂量或年龄组如何，并且在队列 1a 中进一步增加至 57 天，滴度（GMT，288 至 488）升高。在至少第 71 天，滴度仍保持稳定。第二剂疫苗可使滴度增加 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。在第 15 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，明显偏向 1 型辅助 T 细胞。CD8+T 细胞反应总体较强，但在队列 3 中较低。
结论：Ad26.COV2.S 的安全性和免疫原性特征支持进一步开发该疫苗候选物。（由强生公司和美国卫生与公众服务部生物医学高级研究与发展局资助；COV1001 ClinicalTrials.gov 编号，NCT04436276。）
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