Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19
Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19
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DOI：
10.1001/jama.2021.3645
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发表时间：
2021-03-11
影响因子：
120.7
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
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作者：
Stephenson, Kathryn E.;Le Gars, Mathieu;Barouch, Dan H.
重要性控制全球COVID-19大流行将需要开发和部署安全有效的疫苗。目的评价Ad 26. COV 2. S疫苗的免疫原性（Janssen/约翰逊&约翰逊）在人类中的研究，包括SARS-CoV-2刺突特异性体液和细胞免疫应答的动力学、幅度和表型。2020年8月7日，第71天中期分析的随访于2020年10月3日完成;评估耐久性的随访将持续2年。本研究在马萨诸塞州波士顿的一个临床研究中心进行，作为随机、双盲、Ad26.COV2.S.INTERVENTS的安慰剂对照1期临床试验参与者被随机分配接受1或2次肌肉注射，在第1天和第57天给予5 × 1010病毒颗粒或1 × 1011病毒颗粒的Ad26.COV2.S疫苗或安慰剂主要结果和测量体液免疫应答包括免疫后多个时间点的结合和中和抗体应答。细胞免疫反应包括免疫斑点为基础的细胞内细胞因子染色测定，以衡量T细胞responses.Results二十五名参与者被随机（中位年龄，42岁;年龄范围，22-52; 52%的女性，44%的男性，4%未分化），并通过第71天的中期终点完成了试验。结合和中和抗体迅速出现后第8天，分别在90%和25%的疫苗接种者。到第57天，在单次免疫后，在100%的疫苗接种者中检测到结合和中和抗体。第71天，接种组中加标特异性结合抗体的几何平均滴度为2432 - 5729，中和抗体的几何平均滴度为242 - 449。诱导了多种抗体亚类、Fc受体结合特性和抗病毒功能。结论和相关性在该第1阶段研究中，用Ad26.COV2.S单次免疫诱导快速结合和中和抗体应答以及细胞免疫应答。目前正在进行两项3期临床试验，以确定Ad26.COV2.S疫苗的有效性。
IMPORTANCE Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines.OBJECTIVE To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses.DESIGN, SETTING, AND PARTICIPANTS Twenty-five participantswere enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S.INTERVENTIONS Participants were randomized to receive 1 or 2 intramuscular injections with 5 x 1010 viral particles or 1 x 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group).MAIN OUTCOMES AND MEASURES Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses.RESULTS Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced.CONCLUSION AND RELEVANCE In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.