Immunogenicity and safety of BNT162b2 mRNA vaccine in Chinese adults: A phase 2 randomised clinical trial

Abstract

Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited.

Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart. Study participants, study personnel, investigators, statisticians, and the sponsor's study management team were blinded to treatment assignment. Primary immunogenicity endpoints were the geometric mean titers (GMTs) of neutralising antibodies to live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seroconversion rates (SCR) 1 month after the second dose. Safety assessments included reactogenicity within 14 days of vaccination, adverse events (AEs), and clinical laboratory parameters. Randomised participants who received at least one dose were included in the efficacy and safety analyses on a complete case basis (incomplete/missing data not imputed). Results up to 6 months after the second dose are reported.

Findings: Overall, 959 participants (all of Han ethnicity) who were recruited between December 5th, 2020 and January 9th, 2021 received at least one injection (BNT162b2, n=720; placebo, n=239). At 1 month after the second dose, the 50% neutralising antibody GMT was 294.4 (95% CI; 281.1-308.4) in the BNT162b2 group and 5.0 (95% CI; 5.0-5.0) in the placebo group. SCRs were 99.7% (95% CI; 99.0%-100.0%) and 0% (95% CI; 0.0%-1.5%), respectively (p<0.0001 vs placebo). Although the GMT of neutralising antibodies in the BNT162b2 group was greatly reduced at 6 months after the second dose, the SCR still remained at 58.8%. BNT162b2-elicited sera neutralised SARS-CoV-2 variants of concern. T-cell responses were detected in 58/73 (79.5%) BNT162b2 recipients. Reactogenicity was mild or moderate in severity and resolved within a few days after onset. Unsolicited AEs were uncommon at 1 month following vaccine administration, and there were no vaccine-related serious AEs at 1 month or 6 months after the second dose.

Interpretation: BNT162b2 vaccination induced a robust immune response with acceptable tolerability in Han Chinese adults. However, follow-up duration was relatively short and COVID-19 rates were not assessed. Safety data collection is continuing until 12 months after the second dose.

Funding: BioNTech - sponsored the trial. Shanghai Fosun Pharmaceutical Development Inc. (Fosun Pharma) - conducted the trial, funded medical writing.

Clinicaltrialsgov registration number: NCT04649021. Trial status: Completed.

Keywords: BNT162b2 mRNA vaccine; COVID-19; Intramuscular injection; Messenger RNA; Neutralising antibodies; SARS-CoV-2; Vaccination.

Figure 1

Disposition of subjects in the trial. The intent-to-treat (ITT) population and safety population included all participants who underwent randomisation and received at least one dose of study drug.

Figure 2

BNT162b2-induced antibody responses and T-cell responses. Panel a shows BNT162b2-induced neutralising antibody responses at various time-points after the second dose compared with baseline; Panel b shows the ratios of the 50% virus neutralising titers (VNT₅₀) for the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, and Delta to the wild-type strain VNT₅₀; Panel c shows BNT162b2-induced S1-binding immunoglobulin G (IgG) responses at various time-points after the second dose compared with baseline; Panel d shows the Pearson correlation between the VNT₅₀ values (from Panel a) and the spike protein (S1)-binding IgG geometric mean titers (GMTs) (from Panel c); and Panels e1, e2 and f show BNT162b2-induced T-cell responses at various time-points after the second dose compared with baseline. Further detail regarding the time points specified in this figure can be found in Supplementary Figure S1, which presents the vaccination and serum sampling schedule. In Panels a and c, functional 50% SARS-CoV-2 neutralising antibody GMTs, and IgG GMTs, as well as 95% confidence intervals, were plotted. In Panel b, geometric mean ratios (horizontal lines; numbers above data points) were calculated from the individual VNT₅₀ ratios of the Alpha, Beta, and Delta SARS-CoV-2 variants to the wild-type strain, confidence intervals are indicated on the graph by errors bars. Sera for these cross-neutralisation analyses were drawn 1 month after the second dose of BNT162b2. The clinical isolate Italy-INMI1/2020 was used as the wild-type virus in this analysis. In Panel d, the square data points represent individual values outside the lower limit of quantitation. Calculation of the correlation coefficient (r) excluded any values above or below the limits of quantitation. Results shown in Panels e1, e2 and f are from interferon-γ (IFNɣ) enzyme-linked immune absorbent spot (ELISpot) assays conducted on peripheral blood mononuclear cells obtained from participants (n=74, 18–85 years) at baseline (pre-vaccination) and 1 week after the second dose, which were stimulated overnight with overlapping S peptide pools (S pool 1 [Sp1] and S pool 2 [Sp2]). Each data point in Panels e to f represents the mean spot count from quadruple wells for one study participant, after subtraction of the medium-only control. If the spot count was less than one, it was reset to one. Values above each group of data points are the geometric mean spot count of all participants in that group, indicated by a horizontal bar (with error bars indicating the 95% confidence intervals). Panels e1 and e2 show S-specific T-cells (Sp1 and Sp2) producing IFNɣ as a fraction of peripheral blood mononuclear cells (PBMCs) from baseline, and 1 week after the second dose, by age group. Panel f shows T-cell responses to Sp1, Sp2 and to the recall antigen (CEF).

Figure 3

The incidence of solicited local reactions (Panel a) and systemic reactions (Panel b) by maximum severity within 7 days after each dose of BNT162b2 30 μg or placebo. In both Panels a and b, the number above each column is the overall incidence (grade 1–3), and data are for subsets of the safety population by doses received: the safety population for dose one included recipients of the first dose (n=959) and for dose two, recipients of both doses (n=952). Grade 1 reactions were labelled mild and grade 2 moderate, and in Panel b, grade 3 severe. Grading was per the United States Food and Drug Administration criteria. “Related” means “possibly related”, “probably related” or “definitely related” to randomised treatment.