Safety and immunogenicity of SpikoGen®, an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: a phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations

Abstract

Objective: We aimed to investigate the immunogenicity and safety of SpikoGen®, a subunit COVID-19 vaccine composed of a recombinant prefusion-stabilized SARS-CoV-2 spike protein combined with the Advax-CpG55.2™ adjuvant, in seronegative and seropositive populations as primary vaccination.

Methods: This randomized, placebo-controlled, double-blind phase 2 trial was conducted on 400 participants randomized 3:1 to receive two doses of 25 μg of SpikoGen® 3 weeks apart or the placebo. The primary safety outcomes were the incidence of solicited adverse events up to 7 days after each dose and unsolicited adverse events up to 28 days after the second dose. The primary immunogenicity outcomes were seroconversion against the S₁ protein and the geometric mean concentration of S₁ antibodies by days 21 and 35.

Results: The SpikoGen® vaccine was well tolerated and no serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, largely graded as mild and transient. By day 35 (2 weeks post second dose), the seroconversion rate against S₁ was 63.55 (95% CI: 57.81-69.01) in the SpikoGen® group versus 7.23 (95% CI: 2.7-15.07) in the placebo group. The geometric mean concentration of S₁ antibodies was 29.12 (95% CI: 24.32-34.87) in the SpikoGen® group versus 5.53 (95% CI: 4.39-6.97) in the placebo group. Previously infected seropositive volunteers showed a large SARS-CoV-2 humoral response after a single SpikoGen® dose.

Discussion: SpikoGen® had an acceptable safety profile and induced promising humoral and cellular immune responses against SARS-CoV-2.

Keywords: Advax-CpG; COVID-19; Phase 2; SARS-CoV-2; SpikoGen; Subunit protein vaccine.

Fig. 1

Flowchart of screening, randomization, and analysis of the participants. There was an individual who received an incorrect injection during the study. This volunteer in the SpikoGen® group received a single dose of placebo by error and did not receive the vaccine. The participant was included in the placebo safety population. This participant also developed COVID-19 and therefore was excluded from the Per Protocol analysis.

Fig. 2

Solicited local and systemic AEs. The percentage of participants in each group (SpikoGen®, Placebo) with Adverse Events (AEs) according to the maximum Food and Drug Administration (FDA) toxicity grading scale during the 7 days after each vaccination is plotted for solicited local (Panel A) and systemic (Panel B) adverse events. There was no grade 4 (life-threatening) event.

Fig. 3

Shown are geometric mean concentrations (GMCs) in the per-protocol set for S₁ IgG responses (Panel A), receptor binding domain IgG responses (Panel B), and surrogate virus neutralization test responses (Panel C) at day 21 (day of the second injection) and day 35 (14 days after the second injection). Antibody values below the lower limit of quantification (LLOQ) were replaced by 0.5 × LLOQ. The 95% CI was calculated based on the t-distribution of the log-transformed values for GMC levels, then back transformed to the original scale for presentation. For each group, geometric means are depicted above the scatterplot.

Fig. 4

T cell response after stimulation with spike peptide pools. Shown are interferon-γ release after stimulation with AG1 (Panel A), and AG2 (Panel B), fold rise in Interferon-γ concentrations after stimulation with AG1 (Panel C) and AG2 (Panel D). Data are presented as median and interquartile range.