Interim analysis of a phase 1 randomized clinical trial on the safety and immunogenicity of the mRNA-1283 SARS-CoV-2 vaccine in adults

Abstract

This interim analysis of an ongoing phase 1 randomized clinical trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1283, a next-generation SARS-CoV-2 messenger RNA (mRNA)-based vaccine encoding two segments of the spike protein (i.e. receptor binding and N-terminal domains). Healthy adults aged 18-55 years (n = 104) were randomized (1:1:1:1:1) to receive two doses of mRNA-1283 (10, 30, or 100 µg) or mRNA-1273 (100 µg) administered 28 days apart, or a single dose of mRNA-1283 (100 µg). Safety was assessed and immunogenicity was measured by serum neutralizing antibody (nAb) or binding antibody (bAb) responses. At the interim analysis, no safety concerns were identified and no serious adverse events, adverse events of special interest, or deaths were reported. Solicited systemic adverse reactions were more frequent with higher dose levels of mRNA-1283 than with mRNA-1273. At day 57, all dose levels of the 2-dose mRNA-1283 regimen (including the lowest dose level [10 µg]) induced robust nAb and bAb responses that were comparable to those of mRNA-1273 (100 µg). mRNA-1283 was generally safe in adults, with all dose levels of the 2-dose regimen (10, 30, and 100 µg) eliciting similar immunogenicity as the 2-dose mRNA-1273 regimen (100 µg).Clinical Trials Registration: Clinicaltrials.gov, NCT04813796.

Keywords: COVID-19; Severe acute respiratory syndrome coronavirus-2; clinical study; mRNA vaccines; vaccination.

Figure 1.

Participant disposition. One participant in the mRNA-1273 100-µg group discontinued vaccination because of an adverse event, which was considered related to study vaccination. All randomly assigned participants who received dose 1 of the study vaccination were included in the safety population. Reasons for exclusion from the per-protocol immunogenicity population are described in the Supplement. Abbreviation: mRNA, messenger RNA.

Figure 2.

Solicited (a) local and (b) systemic adverse reactions within 7 days of each dose. Percentages are based on participants in the solicited safety population, consisting of all randomly assigned participants receiving ≥1 dose and contributing any solicited adverse reaction data. Number of participants in the dose 1 solicited safety population: mRNA-1283 10 µg, n = 21; mRNA-1283 30 µg, n = 22; mRNA-1283 100 µg, n = 21; placebo + mRNA-1283 100 µg, n = 18; and mRNA-1273 100 µg, n = 22. Number of participants in the dose 2 solicited safety population: mRNA-1283 10 µg, n = 19; mRNA-1283 30 µg, n = 20; mRNA-1283 100 µg, n = 21; placebo + mRNA-1283 100 µg, n = 15; and mRNA-1273 100 µg, n = 20. Abbreviation: mRNA, messenger RNA.

Figure 3.

Pseudovirus neutralizing antibody ID₅₀ titers against (a) Wuhan-Hu-1 (with D614G mutation) SARS-CoV-2 or (b) B.1.351 variant through day 57. Neutralizing antibody titers on the pseudovirus neutralization assay at ID₅₀ (log scale) are shown for those participants in the per-protocol immunogenicity population. In both panels, boxplots are based on log-transformed values; boxes and horizontal bars denote IQR range and ID₅₀, respectively, with whisker end points equal to the values below or above the median at 1.5 times the IQR. Dots represent individual results and the dotted lines represent either the LLOQ or ULOQ. Antibody values reported as below the LLOQ were replaced by 0.5 × LLOQ, whereas values greater than the ULOQ were converted to the ULOQ if the actual values were unavailable. In panel a, the LLOQ was 18.5 (log₁₀[LLOQ] = 1.267) and the ULOQ was 45,118 (log₁₀[ULOQ] = 4.654). In panel b, the LLOQ was 19.5 (log₁₀[LLOQ] = 1.290) and the ULOQ was 385.7 (log₁₀[ULOQ] = 2.586).

Figure 4.

Binding antibody levels through day 57 specific to Wuhan-Hu-1 SARS-CoV-2 (a) S protein, (b) RBD, or (C) NTD Binding IgG antibody levels by MSD 4-PLEX assay are shown for those participants in the per-protocol immunogenicity population. Boxplots are based on log-transformed values; boxes and horizontal bars denote IQR range and GM, respectively, with whisker end points equal to the values below or above the median at 1.5 times the IQR. Individual results are represented as dots and the dotted lines represent either the LLOQ or ULOQ. Antibody values reported as below the LLOQ were replaced by 0.5 × LLOQ, whereas values greater than the ULOQ were converted to the ULOQ if actual values were unavailable. In panel a, the LLOQ was 23 (log₁₀[LLOQ] = 1.362) and the ULOQ was 14,000,000 (log₁₀[ULOQ] = 7.146). In panel b, the LLOQ was 19 (log₁₀[LLOQ] = 1.279) and the ULOQ was 6,000,000 (log₁₀[ULOQ] = 6.778). In panel c, the LLOQ was 3 (log₁₀[LLOQ] = 0.477) and the ULOQ was 200000 (log₁₀[ULOQ] = 5.301).