Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial

Abstract

Background Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of ...

Rapid development of an updated mRNA vaccine against the SARS-CoV-2 Omicron variant

“…1a), it is interesting to assess the neutralizing activity of serum samples from vaccinees of ARCoV against the Omicron variant. To do so, a panel of serum samples (n = 11) from participants in the phase 1 clinical trial 10 were analyzed for their neutralizing Ab titers using VSV-based pseudovirus. All samples were collected on day 14 post two-dose immunization with 15 µg of ARCoV.…”

Safety and superior immunogenicity of heterologous boosting with an RBD-based SARS-CoV-2 mRNA vaccine in Chinese adults

“…Collectively, our present study clearly demonstrated that a 3 rd dose of heterologous boosting with AWcorna was safe and potential protective against the circulating Delta and Omicron variants. Compared with phase 1 trial, the total IRs of local and systemic AEs for AWcorna booster showed significant improvement 10 , especially the IR of grade 3 fever reduced to 4% (Supplementary information, Table S4 ), which was comparable to the other two approved mRNA vaccines 11 . The phase 1 trial of AWcorna only included 20 adults aged 18-59 (15 μg group), while our present cohort enrolled 200 participants, including 10 subjects aged over 60.…”

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.…”