Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials.
10.1097/CM9.0000000000001573
- VernacularTitle:Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials
- Author:
Hong-Xing PAN
1
;
Jian-Kai LIU
2
;
Bao-Ying HUANG
3
;
Gui-Fan LI
4
;
Xian-Yun CHANG
4
;
Ya-Fei LIU
4
;
Wen-Ling WANG
3
;
Kai CHU
1
;
Jia-Lei HU
1
;
Jing-Xin LI
1
;
Dan-Dan ZHU
5
;
Jing-Liang WU
5
;
Xiao-Yu XU
6
;
Li ZHANG
7
;
Meng WANG
7
;
Wen-Jie TAN
3
;
Wei-Jin HUANG
7
;
Feng-Cai ZHU
1
Author Information
1. NHC Key Laboratory of Enteric Pathogenic Microbiology (Jiangsu Provincial Center for Disease Control and Prevention), Nanjing, Jiangsu 210009, China.
2. Shenzhen Kangtai Biological Products Co., Ltd., Shenzhen, Guangdong 518057, China.
3. NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
4. Beijing Minhai Biological Technology Co., Ltd., Beijing 102600, China.
5. Huaiyin District Center for Disease Control and Prevention, Huai'an, Jiangsu 223003, China.
6. Vazyme Biotech Co., Ltd, Nanjing, Jiangsu 210000, China.
7. National Institutes for Food and Drug Control, Beijing 102629, China.
- Publication Type:Randomized Controlled Trial
- MeSH:
Adult;
COVID-19;
COVID-19 Vaccines;
Double-Blind Method;
Humans;
SARS-CoV-2;
Vaccines, Inactivated/adverse effects*
- From:
Chinese Medical Journal
2021;134(11):1289-1298
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.
METHODS:Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.
RESULTS:In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.
CONCLUSIONS:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.
TRIAL REGISTRATION:http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
