Safety and immunogenicity of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine (MVC-COV1901) Adjuvanted with CpG 1018 and Aluminum Hydroxide in healthy adults: A Phase 1, dose-escalation study

Abstract

Background: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018.

Methods: Between September 28 and November 13 2020, 77 participants were screened. Of these, 45 healthy adults from 20 to 49 years of age were to be administered two doses of MVC-COV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second dose at the time of the interim analysis. Adverse events and laboratory data were recorded for the safety evaluation. Blood samples were collected for humoral, and cellular immune response at various time points. Trial Registration: ClinicalTrials.gov NCT04487210.

Findings: Solicited adverse events were mostly mild and similar. No subject experienced fever. After the second dose, the geometric mean titers (GMTs) for SARS-CoV-2 spike-specific immunoglobulin G were 7178.2, 7746.1, 11,220.6 in the 5 μg, 15 μg, and 25 μg dose groups, respectively. The neutralizing activity were detected in both methods. (Day 43 GMTs, 538.5, 993.1, and 1905.8 for pseudovirus; and 33.3, 76.3, and 167.4 for wild-type virus). The cellular immune response induced by MVC-COV1901 demonstrated substantially higher numbers of IFN-γ- producing cells, suggesting a Th1-skewed immune response.

Interpretation: The MVC-COV1901 vaccine was well tolerated and elicited robust immune responses and is suitable for further development.

Funding: Medigen Vaccine Biologics Corporation.

Fig. 1

Consort Flow Diagram.

Fig. 2

Summary of Solicited Adverse Events Participants were asked to record solicited local and systemic adverse events in the participant's diary card for up to 7 days after each vaccination. Solicited AEs were tabulated and graded as mild, moderate, or severe.

Fig. 3

Summary of Humoral Immune Response Sera of participants vaccinated with 5, 15, or 25 μg of MVC—COV1901 were measured for anti-spike IgG by (A) ELISA, and neutralization titers were measured by (B) pseudovirus neutralization assay or (C) live virus neutralization assay. Human convalescent sera (HCS) from 35 recovered COVID-19 patients were analysed by the same assays for comparison and NIBSC 20/130 standard was used in the live virus neutralization assay as a standard (asterisk in panel C). Bars indicate geometric mean titers and error bars indicate 95% confidence intervals. A: The SARS-CoV-2 spike specific IgG GMTs at Day 43 were 7178.2 (5 μg), 7746.1 (15 μg), 11,220.6 (25 μg), and 2179.6 (HCS); B: The SARS-CoV-2 pseudovirus ID₅₀ GMTs at Day 43 were 538.5 (5 μg), 993.1 (15 μg), 1905.8 (25 μg), and 430.5 (HCS); C: The wild type SARS-CoV-2 NT₅₀ GMTs at Day 43 were 33.3 (5 μg), 76.3 (15 μg), 167.4 (25 μg), and 42.7 (HCS) as detailed in Table S4. The value of NIBSC 20/130 standard was 281.8. (asterisk).

Fig. 4

Summary of Cellular Immune Response Cells were stimulated with a S1 peptides pool of peptides and incubated at 37⁰C for 24–48 h. Cells stimulated with CD3–2 mAb served as a positive control. IFN-γ (left) or IL-4 (right) were detected using an ELISpot assay. The mean of spot-forming units (SFU) counted in peptide pool stimulation triplicate was calculated and normalized by subtracting the mean of the negative control replicates (control media). Results were expressed as SFU per million PBMC. Bars indicate the mean values and error bars indicate standard deviations.