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新冠疫苗Ad26.COV2.S的临床1期试验分析
作者:小柯机器人 发布时间:2021/3/14 23:24:11

美国贝丝以色列女执事医疗中心Dan H. Barouch团队研究了新冠病毒Ad26.COV2.S疫苗的免疫原性。2021年3月11日,《美国医学会杂志》发表了该成果。

控制COVID-19全球大流行需要开发和部署安全有效的疫苗。

为了评价Ad26.COV2.S疫苗(美国强生公司)在人体内的免疫原性,包括SARS-CoV-2刺突蛋白特异性体液和细胞免疫反应的动力学、强度和表型,2020年7月29日至2020年8月7日,研究组在马萨诸塞州波士顿的一个单一临床机构进行了Ad26.COV2.S的随机、双盲、安慰剂对照、1期临床试验的一部分。共招募了25名参与者,并于2020年10月3日完成了第71天中期分析的随访。

将参与者随机分组,分别接受1或2次肌肉注射5×1010病毒颗粒或1×1011病毒颗粒的Ad26.COV2.S疫苗或安慰剂(每组5名参与者)。主要结果为体液免疫反应,包括免疫后多个时间点的结合和中和抗体反应。细胞免疫反应包括免疫斑点法和细胞内细胞因子染色法。

25名受试者的中位年龄为42岁,52%为女性,44%为男性,4%性别不明,所有受试者均在第71天结束时完成试验。初次免疫后第8天,90%和25%的疫苗接种者体内迅速出现结合抗体和中和抗体。到第57天,单次免疫后100%的疫苗接种者均检测到结合抗体和中和抗体。在第71天,免疫组的刺突蛋白特异性结合抗体的几何平均滴度为2432至5729,中和抗体的几何平均滴度为242至449。诱导了多种抗体亚类、Fc受体结合特性和抗病毒功能,还诱导了CD4+和CD8+T细胞应答。

研究结果表明,在临床1期研究中,用Ad26.COV2.S单次免疫可诱导快速结合抗体和中和抗体应答,以及细胞免疫应答。

附:英文原文

Title: Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19

Author: Kathryn E. Stephenson, Mathieu Le Gars, Jerald Sadoff, Anne Marit de Groot, Dirk Heerwegh, Carla Truyers, Caroline Atyeo, Carolin Loos, Abishek Chandrashekar, Katherine McMahan, Lisa H. Tostanoski, Jingyou Yu, Makda S. Gebre, Catherine Jacob-Dolan, Zhenfeng Li, Shivani Patel, Lauren Peter, Jinyan Liu, Erica N. Borducchi, Joseph P. Nkolola, Morgana Souza, Chen Sabrina Tan, Rebecca Zash, Boris Julg, Ruvandhi R. Nathavitharana, Roger L. Shapiro, Ahmed Abdul Azim, Carolyn D. Alonso, Kate Jaegle, Jessica L. Ansel, Diane G. Kanjilal, Caitlin J. Guiney, Connor Bradshaw, Anna Tyler, Tatenda Makoni, Katherine E. Yanosick, Michael S. Seaman, Douglas A. Lauffenburger, Galit Alter, Frank Struyf, Macaya Douoguih, Johan Van Hoof, Hanneke Schuitemaker, Dan H. Barouch

Issue&Volume: 2021-03-11

Abstract:

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 participants were 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 5×1010 viral particles or 1×1011 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.

DOI: 10.1001/jama.2021.3645

Source: https://jamanetwork.com/journals/jama/fullarticle/2777598

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex