Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials

Abstract

Background Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study. Methods We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18–59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov ( NCT04445194 and NCT04466085 ) and participant follow-up is ongoing. Findings Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90...

Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines

“…ZF2001 is an RBD-dimer subunit vaccine that has been authorized to be deployed in China and Uzbekistan. 11,12 Twenty ZF2001 vaccinee volunteers (designated as R1-R20) were also recruited after a 0/30/60 three-dose vaccination (n = 10) or a 0/30/140 extended third-dose vaccination (n = 10). None of the volunteers was prior infected by SARS-CoV-2.…”

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial

“…According to the draft landscape of COVID-19 candidate vaccines by the World Health Organizations (WHO), there were over 185 candidate vaccines in preclinical evaluations and 102 undergoing clinical evaluations in different phases till June 8 [2] . Among them, the results of phase 1/2 trials of 24 candidate vaccines have been published or made available on preprint servers, including seven protein subunit [3] , [4] , [5] , [6] , [7] , [8] , [9] , six inactivated [10] , [11] , [12] , [13] , [14] , [15] , six recombinant, [16] , [17] , [18] , [19] , [20] , [21] three mRNA, [22] , [23] , [24] one DNA vaccine, [25] and one virus-like particle vaccine [26] . All 24 vaccines demonstrated acceptable safety profiles and immunogenicity.…”

What do we know about China’s covid-19 vaccines?

“…The trials found immunogenicity in most patients and that the vaccine was generally safe and well tolerated, with few adverse effects. Phase I and II data for the Anhui Zhifei Longcom vaccine published in March4 showed similar results.…”