A randomized, double-blind, placebo-controlled phase 1 and phase 2 clinical trial to evaluate efficacy and safety of a SARS-CoV-2 vaccine SCoK in adults

Deyan Luo, Hongxing Pan, Peng He, Xiaolan Yang, Tao Li, Nianzhi Ning, Xin Fang, Wenjing Yu, Mingwei Wei, Hui Gao, Xin Wang, Hongjing Gu, Maodong Mei, Xinwang Li, Liangyan Zhang, Deyu Li, Chunrun Gao, Jinbang Gao, Guoqiang Fei, Ying Li, Yuguo Yang, Yi Xu, Wenjin Wei, Yansong Sun, Fengcai Zhu, Zhongyu Hu, Hui Wang, Deyan Luo, Hongxing Pan, Peng He, Xiaolan Yang, Tao Li, Nianzhi Ning, Xin Fang, Wenjing Yu, Mingwei Wei, Hui Gao, Xin Wang, Hongjing Gu, Maodong Mei, Xinwang Li, Liangyan Zhang, Deyu Li, Chunrun Gao, Jinbang Gao, Guoqiang Fei, Ying Li, Yuguo Yang, Yi Xu, Wenjin Wei, Yansong Sun, Fengcai Zhu, Zhongyu Hu, Hui Wang

Abstract

Background: To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID-19 for an efficacy study; herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults.

Methods: These randomized, double-blind, placebo-controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 μg vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo.

Results: No serious vaccine-related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS-CoV-2. The vaccine induced significant neutralizing antibody responses to live SARS-CoV-2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 μg doses, respectively; the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic.

Trial registration: ClinicalTrials.gov NCT04636333 NCT04813562.

Keywords: SARS-CoV-2; clinical trial; safety; vaccine SCoK.

Conflict of interest statement

None of the authors have any competing interests to declare.

© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

Figures

FIGURE 1
FIGURE 1
Study protocol for phase 1 and 2 trials. Reasons for exclusion of 10 participants (one in phase 1, and nine in phase 2) from the according‐to‐protocol cohort for vaccination and immunogenicity analysis are listed in Supporting Information 2
FIGURE 2
FIGURE 2
Humoral immune responses in phase 1. Geometric mean titres (GMTs) of RBD binding antibody (A, B, and C), neutralizing antibody titres against pseudovirus (D, E, and F), and neutralizing antibody titres against live virus (G, H, and I) assessed at different time points after the first vaccination are shown. Seroconversion rates are shown at the top of each figure. Horizontal dashed line indicates limit of detection. Analysis of variance (ANOVA) was used to analyse log‐transformed antibody titers.*p < .05, **p < .01, *** p< .001, ****p < .0001
FIGURE 3
FIGURE 3
Humoral immune responses in phase 2. GMTs of RBD binding antibody (A and B), neutralizing antibody titres against pseudovirus (C and D), and neutralizing antibody titres against live virus (E and F) assessed at different time points after the first vaccination are shown. Seroconversion rates are shown at the top of each figure. Horizontal dashed line indicates limit of detection. Analysis of variance (ANOVA) was used to analyse log‐transformed antibody titres. *p < .05, **p < .01, ***p < .001, ****p < .0001

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