tetano
Editor, Senior Moderator
Chin Med J (Engl)
. 2021 Apr 28.
doi: 10.1097/CM9.0000000000001573. Online ahead of print.
Immunogenicity and safety of a SARS-CoV-2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials
Hong-Xing Pan[SUP] 1 [/SUP], Jian-Kai Liu, Bao-Ying Huang, Gui-Fan Li, Xian-Yun Chang, Ya-Fei Liu, Wen-Ling Wang, Kai Chu, Jia-Lei Hu, Jing-Xin Li, Dan-Dan Zhu, Jing-Liang Wu, Xiao-Yu Xu, Li Zhang, Meng Wang, Wen-Jie Tan, Wei-Jin Huang, Feng-Cai Zhu
Affiliations
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 18-59 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 ?g/dose or 10 ?g/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 ?g/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-?g vaccine (n = 24), 10-?g vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-?g vaccine (n = 100 for 0/14 or 0/28 regimens), 10-?g vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and 7 (58%) participants reported at least one adverse event (AE) after receiving 5-?g vaccine, 10-?g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) 0/14-regimen participants reported at least one AE after receiving 5-?g vaccine, 10-?g 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-?g 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).
. 2021 Apr 28.
doi: 10.1097/CM9.0000000000001573. Online ahead of print.
Immunogenicity and safety of a SARS-CoV-2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials
Hong-Xing Pan[SUP] 1 [/SUP], Jian-Kai Liu, Bao-Ying Huang, Gui-Fan Li, Xian-Yun Chang, Ya-Fei Liu, Wen-Ling Wang, Kai Chu, Jia-Lei Hu, Jing-Xin Li, Dan-Dan Zhu, Jing-Liang Wu, Xiao-Yu Xu, Li Zhang, Meng Wang, Wen-Jie Tan, Wei-Jin Huang, Feng-Cai Zhu
Affiliations
- PMID: 33928916
- DOI: 10.1097/CM9.0000000000001573
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 18-59 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 ?g/dose or 10 ?g/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 ?g/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-?g vaccine (n = 24), 10-?g vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-?g vaccine (n = 100 for 0/14 or 0/28 regimens), 10-?g vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and 7 (58%) participants reported at least one adverse event (AE) after receiving 5-?g vaccine, 10-?g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) 0/14-regimen participants reported at least one AE after receiving 5-?g vaccine, 10-?g 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-?g 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).