Safety and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older: two single-center, randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials

Abstract

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9–171.2) and 102.6 (95% CI 75.2–140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.

3-dose of RBD vaccine is sufficient to elicit a long-lasting memory response against SARS-CoV-2 infection

“…A variety of vaccines, including the mRNA and recombinant vaccines, were developed to prevent the spread of the disease. 1 , 2 There is an urgent need for testing the vaccine-induced long-term memory response based on the immunological principles and identifying the optimal combination of dose and injection manner to provide important information for clinical application.…”

The Impact of COVID-19 and Vaccine on the Human Nervous System

“…Then, the literature was screened by the following criteria: (1) healthy participants older than 16 years; (2) a sample size of at least 100 participants; (3) randomized controlled design; and (4) the most recent study phase. A total of 33 studies met the inclusion criteria [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ], and we extracted the vaccine platform, name, location, age, study phase, sample size, and safety data (especially the neurological AEs) from the included clinical trials (Table 2 ). Moreover, it must be noted that vaccine-unrelated AEs as specified in the articles have been excluded.…”

Adverse Events Reporting Quality of Randomized Controlled Trials of COVID-19 Vaccine Using the CONSORT Criteria for Reporting Harms: A Systematic Review

“…The risk of bias was analyzed using the RoB 2 tools for 61 trials included in this review. Among them, 12 clinical trials scored as "high-risk" [19,33,34,39,40,46,47,49,[53][54][55]77]; 28 trials categorized as trials with 'some concerns'; while the remaining trials (21 studies) were classified as "low-risk" (Figure 2). Four studies were identified with the most "highrisk" due to unconcealed intervention to the participants and outcome measure affected by the knowledge of investigators [46,47,54,55].…”

“…A total of 36 studies (59.02%) adhered with the CONSORT recommendation for reporting harms, with the two highest studies reporting 20 score of 21 THRS, as shown in Table 2. The most significant domain that induced the high-risk judgment was biased in measurement of the outcome (domain 4) [33,34,40,46,47,49,[53][54][55]. There were concerns that the clinical trial outcome would be affected by prior knowledge of the outcome assessor.…”