Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 were enrolled in the phase 1 trial (figure 1). There were 20 participants in each of the vaccine dose groups and the placebo group. All 120 participants received at least one dose of the vaccine or placebo and were included in the safety analysis. Four participants withdrew, none due to adverse events (two withdrew voluntarily after first vaccination, two withdrew after second vaccination; appendix p 15). 116 participants were eligible for immunogenic assessment.

The median age of participants was 27·0 years (IQR 22·0–34·8), and mean body-mass index was 24·2 kg/m² (SD 3·1). Of 120 participants, 75 (62·5%) were male sex and 45 (37·5%) female sex. Overall male to female ratio was 5:3. The majority of participants (118 [98%]) were of the Han ethnic group. One participant with a history of hypertension was enrolled in the 5 μg dose group. Baseline demographic characteristics of the participants at enrolment were similar among the treatment groups in terms of median age, ethnic group, body-mass index, and medical history or pre-existing conditions (gender ratio of participants χ²=8·00, ν=1; table 1).

Adverse events were graded according to the guidelines for vaccine clinical trials issued by the US FDA and the China National Medical Products Administration (Table 2, Table 3). 7 days after first or second vaccination, reactogenicity was partly dose-related (table 2). The incidence of solicited adverse events was 12 (60%) of 20 in the 5 μg group, 16 (80%) of 20 in the 10 μg group, 19 (95%) of 20 in the 15 μg group, 19 (95%) of 20 in the 20 μg group, and 16 (100%) of 16 in the 25 μg group, compared with one (5%) of 20 in the placebo group. The most common solicited adverse reactions reported were injection site pain, fever, headache, fatigue or malaise, injection site redness, muscle pain, injection site induration and itch, joint pain, diarrhoea, and chills (Table 2, Table 3). Adverse events after first or second vaccination were transient and managed with simple standard medication or care, or resolved spontaneously (appendix pp 16–18). Most reported adverse reactions were mild or moderate in severity and about 95% resolved in the first 2 days after first or second vaccinations: the remaining resolved within 5 days. Only one participant developed grade 3 pain in the injection site. Grade 3 fever was the only severe systemic adverse reaction associated with vaccination. No grade 3 fever was reported in the 5 μg group, whereas three (15%) of 20 participants reported grade 3 fever in the 10 μg group. This incidence increased with higher dosage (six [30%] of 20 participants in the 15 μg group, seven [35%] of 20 in the 20 μg group, and six [38%] of 20 in the 25 μg group). Participants who received the placebo had no adverse events except for one who had mild pain at the injection site. The incidence of solicited adverse events after first vaccination, for systemic adverse events and local adverse events, was similar to that after the second vaccination (appendix pp 11–12). For example, the incidence of grade 3 fever after the first vaccination was similar to that after the second vaccination (one [5%] of 20 participants in the 10 μg group, four [20%] of 20 in the 15 μg group, four [20%] of 20 in the 20 μg group, four [20%] of 20 in the 25 μg group vs two [10%] of 20, three [15%] of 20, five [25%] of 20, four [25%] of 16). For fatigue or malaise, headache, and redness compared with the first vaccination, the incidence slightly decreased after the second vaccination (appendix pp 11–12). Additionally, unsolicited adverse events related to vaccination were mild and moderate and mainly included infections (mostly urinary tract infections and upper respiratory tract infections), and kidney and urinary system diseases (mostly albuminuria). Unsolicited adverse events unrelated to vaccination mainly included infections (urinary tract infections, upper respiratory tract infections, nasopharyngitis, conjunctivitis, periodontitis, and otitis media), gastrointestinal disorders (toothache, nausea, diarrhoea, abdominal distension, oral ulcer, and vomit), and nervous system disorders (headache and hypoesthesia; appendix p 10).

During the safety observation, most participants in each vaccination group reported at least one unsolicited adverse reaction. The most common abnormalities were transient decreases in lymphocyte and neutrophil counts; and increases in C-reactive protein concentrations, urinary tract infections, and albuminuria in vaccine participants. Lymphocyte count on day 1 after first or second vaccination significantly reduced in all vaccine groups compared with the placebo group then recovered back to baseline 4 days after first or second vaccination. Additionally, on day 1 after first vaccination, lymphocyte counts increased significantly in the placebo group, which was still within normal clinical range (appendix p 13). All laboratory abnormalities were self-limited and resolved in a short period without clinical symptoms. Results were consistent with lymphocyte counts

and concentrations of C-reactive protein

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• Tsai MY
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• Straka RJ
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Effect of influenza vaccine on markers of inflammation and lipid profile.

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• Doener F
• Hong HS
• Meyer I
• et al.

RNA-based adjuvant CV8102 enhances the immunogenicity of a licensed rabies vaccine in a first-in-human trial.

reported as pharmacodynamics markers after administration of mRNA vaccines against influenza and rabies.