中国生物技术集团有限公司杨晓明团队联合华中科技大学同济医学院潘安教授课题组分析了SARS-CoV-2灭活疫苗的安全性和免疫原性。2020年8月13日，《美国医学会杂志》发表了这一成果。

研发COVID-19疫苗已迫在眉睫。为了评估灭活全病毒COVID-19疫苗的安全性和免疫原性，研究组进行了一项随机、双盲、安慰剂对照的1期和2期临床试验，于2020年4月12日开始，在中国河南省招募18-59岁的健康成年人。

其中1期试验招募了96名参与者，随机分成4组（每组24名），分别在第0、28和56天肌肉注射每剂量2.5μg、5μg、10μg的灭活COVID-19疫苗，或仅氢氧化铝佐剂（铝剂）。2期试验招募了224名参与者，分成两个接种计划组，84名在第0、14天接种每剂量5μg的疫苗，28名仅接种铝剂；另外84名在第0、21天接种每剂量5μg的疫苗，28名仅接种铝剂。

320名参与者的平均年龄为42.8岁，女性占62.5%，均在全程疫苗接种后28天内完成了试验。1期试验中，仅铝剂组、低剂量组、中剂量组和高剂量组中分别有3名（12.5%）、5名（20.8%），4名（16.7%）和6名（25.0%）参与者发生7天内不良反应；在2期试验中，第0、14天接种疫苗组和铝剂组中分别有5名（6.0%）和4名（14.3%）患者，第0、21天接种疫苗组和铝剂组中分别有16名（19.0％）和5名（17.9％）患者发生7天内不良反应。

最常见的不良反应是注射部位疼痛，其次是发烧，均为轻度且自限。未发现严重不良反应。1期试验中，低剂量、中剂量和高剂量组在3次注射后第14天的几何平均滴度分别为316、206和297；2期试验中，在第0、14天和第0、21天接种疫苗的参与者在2次注射后第14天的几何平均滴度分别为121和247。在所有仅注射铝剂组中均未检测到抗体反应。

总之，灭活COVID-19疫苗1期和2期临床试验的中期分析表明，患者不良反应发生率低，且具有免疫原性。仍需进行3期临床试验对疗效和长期不良事件进行评估。

附：英文原文

Title: Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials

Author: Shengli Xia, Kai Duan, Yuntao Zhang, Dongyang Zhao, Huajun Zhang, Zhiqiang Xie, Xinguo Li, Cheng Peng, Yanbo Zhang, Wei Zhang, Yunkai Yang, Wei Chen, Xiaoxiao Gao, Wangyang You, Xuewei Wang, Zejun Wang, Zhengli Shi, Yanxia Wang, Xuqin Yang, Lianghao Zhang, Lili Huang, Qian Wang, Jia Lu, Yongli Yang, Jing Guo, Wei Zhou, Xin Wan, Cong Wu, Wenhui Wang, Shihe Huang, Jianhui Du, Ziyan Meng, An Pan, Zhiming Yuan, Shuo Shen, Wanshen Guo, Xiaoming Yang

Issue&Volume: 2020-08-13

Abstract: Importance  A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed.

Objective  To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China.

Interventions  In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant–only group (n=24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n=84] vs alum only [n=28], and days 0 and 21 [n=84] vs alum only [n=28]).

Design, Setting, and Participants  Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020.

Main Outcomes and Measures  The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results  Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups.

Conclusions and Relevance  In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials.

DOI: 10.1001/jama.2020.15543

Source: https://jamanetwork.com/journals/jama/fullarticle/2769612