18岁及以上健康成年人中一剂新冠DNA疫苗加强针的免疫原性和安全性：一项单中心、随机、观察者盲法、安慰剂对照的2期试验。
Immunogenicity and safety of a booster dose of the COVID-19 DNA vaccine in healthy adults aged 18 years and above: a single-center, randomized, observer-blind, placebo-controlled phase 2 trial.
作者信息
Yao Aihua, Jia Siyue, Cheng Xin, Pan Hongxing, Wang Zhijian, Yang Haitao, Xia Yu, Xu Jianfang, Huai Xuefen, Leng Danjing, Xu Ming, Wang Jiarong, Zhao Gan, Wang Bin, Li Jingxin
机构信息
School of Public Health, Southeast University, Nanjing, China.
Jiangsu Provincial Medical Innovation Center, National Health Commission Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Provincial Academy of Preventive Medicine), 172 Jiangsu Avenue, Nanjing, 210009, China.
出版信息
BMC Infect Dis. 2025 May 25;25(1):750. doi: 10.1186/s12879-025-11140-w.
BACKGROUND
A two-dose primary regimen of INO-4800 DNA vaccine demonstrated only modest immunogenicity in the previous phase 2 clinical trial. This booster study aimed to evaluate the immunogenicity and safety of a booster dose of INO-4800 in adults previously received two-dose regimen of INO-4800.
METHODS
Healthy adults who received two doses of INO-4800 (1.0 mg or 2.0 mg) at least 12 months ago in a previous phase 2 trial were eligible for this booster study, conducted in Danyang, Jiangsu Province, China. Eligible participants were stratified by primary vaccination dose (1.0 mg or 2.0 mg) and age group (18-59 years or ≥ 60 years), and subsequently randomized in a 1:1 ratio to receive a third dose of INO-4800 or placebo at the same dosage as previously administered. The primary immunogenicity endpoint was the geometric mean concentrations (GMCs) of spike-binding antibodies on day 14 post-booster. The primary safety endpoint was the occurrence of adverse reactions within 14 days.
RESULTS
Between December 20 and 23, 2021, 200 eligible participants were enrolled. 100 eligible participants who received two doses of 2.0 mg INO-4800 were randomly assigned (1:1) to receive a third dose of 2.0 mg INO-4800 (n = 50) or 2.0 mg placebo (n = 50). Another 100 eligible participants who received two doses of 1.0 mg INO-4800 were randomly assigned (1:1) to receive a third dose of 1.0 mg INO-4800 (n = 50) or 1.0 mg placebo (n = 50). On day 14 post-booster, the GMCs of spike-binding antibodies were significantly higher in 2.0 mg INO-4800 group ( 260.1 BAU/mL) compared to placebo group (2.8 BAU/mL, p < 0.001), and in 1.0 mg INO-4800 group (104.2 BAU/mL) compared to placebo group (2.5 BAU/mL, p < 0.001). The most common local reactions were injection site redness, occurring at rate of 16.0% in the INO-4800 groups.All adverse reactions were mild to moderate in severity and occurred within 14 days post-booster. No vaccine related serious adverse events were reported.
CONCLUSIONS
The booster regimen of one dose INO-4800 is safe and modestly immunogenic in individuals who previously received a two- dose regimen of INO-4800, with the 2.0 mg INO-4800 demonstrating superior immunogenicity compared to the 1.0 mg INO-4800.
TRIAL REGISTRATION
www.chictr.org.cn , identifier is ChiCTR2100054324.(December 13 2021).
背景
INO-4800 DNA疫苗的两剂次基础免疫方案在前一项2期临床试验中显示出的免疫原性仅为中等水平。这项加强针研究旨在评估在先前接受过两剂次INO-4800免疫的成年人中，一剂次INO-4800加强针的免疫原性和安全性。
方法
在中国江苏省丹阳市开展了这项加强针研究，符合条件的受试者为至少在12个月前的一项2期试验中接受过两剂次INO-4800（1.0毫克或2.0毫克）的健康成年人。符合条件的参与者按基础免疫剂量（1.0毫克或2.0毫克）和年龄组（18至59岁或≥60岁）进行分层，随后按1:1的比例随机分组，接受与之前相同剂量的第三剂INO-4800或安慰剂。主要免疫原性终点是加强针接种后第14天刺突结合抗体的几何平均浓度（GMC）。主要安全性终点是14天内不良反应的发生情况。
结果
2021年12月20日至23日，共纳入200名符合条件的参与者。100名接受过两剂次2.0毫克INO-4800的符合条件参与者被随机分配（1:1）接受第三剂2.0毫克INO-4800（n = 50）或2.0毫克安慰剂（n = 50）。另外100名接受过两剂次1.0毫克INO-4800的符合条件参与者被随机分配（1:1）接受第三剂1.0毫克INO-4800（n = 50）或1.0毫克安慰剂（n = 50）。加强针接种后第14天，2.0毫克INO-4800组（260.1 BAU/mL）的刺突结合抗体GMC显著高于安慰剂组（2.8 BAU/mL，p < 0.001），1.0毫克INO-4800组（104.2 BAU/mL）的刺突结合抗体GMC也显著高于安慰剂组（2.5 BAU/mL，p < 0.001）。最常见的局部反应是注射部位发红，在INO-4800组中的发生率为16.0%。所有不良反应的严重程度均为轻至中度，且发生在加强针接种后的14天内。未报告与疫苗相关的严重不良事件。
结论
对于先前接受过两剂次INO-4800免疫的个体，一剂次INO-4800加强针方案是安全的，且具有一定的免疫原性，2.0毫克INO-4800的免疫原性优于1.0毫克INO-4800。
试验注册
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