Immunogenicity and safety of SpikoGen®, an adjuvanted recombinant SARS-CoV-2 spike protein vaccine as a homologous and heterologous booster vaccination: A randomized placebo-controlled trial

Abstract

SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax-CpG55.2™ adjuvant. This COVID-19 vaccine was shown to be safe, immunogenic and efficacious in previous clinical trials. This study aimed to assess the safety and immunogenicity of SpikoGen® vaccine as a homologous and heterologous booster vaccination. This double-blind and randomized placebo-controlled (5:1) trial was performed on 300 already vaccinated participants. SpikoGen® or saline placebo was administered as a booster dose to participants who had received a full two-dose COVID-19 vaccination course. Immunogenicity assessments were done 14 days after the booster dose with the primary immunogenicity outcome seroconversion rate of neutralizing antibodies. Safety outcomes included the incidence of solicited adverse events up to 7 days after the booster dose. SpikoGen® vaccine induced a robust humoral response both as a homologous and heterologous booster, when compared to the placebo. At Day 14, seroconversion of neutralizing antibodies was 76% (95% confidence interval [CI]: 69%-82%) in the SpikoGen® group versus 3% (95% CI: 0%-13%) in the placebo group. The most common local and systemic reported adverse events were injection site pain and fatigue. No serious adverse events were reported. The SpikoGen®-booster induced cross-neutralization of other SARS-CoV-2 variants. Irrespective of the primary vaccine course received, SpikoGen® vaccine showed promising effects as both a homologous and heterologous booster dose. This vaccine also had a good safety profile with no vaccine-associated serious adverse events. On the basis of these results, SpikoGen® vaccine has been approved as a booster dose.

Keywords: COVID-19; SARS-CoV-2; SpikoGen; booster; cross-neutralization.

FIGURE 1

CONSORT flowchart showing schema of screening, randomization and analysis of participants

FIGURE 2

Shown are geometric mean concentration (GMC) in the per‐protocol set for sVNT_w responses (panel a), S_1w IgG responses (panel b) and RBD_w IgG responses (panel c) at Days 0 and 14 (14 days after the booster dose). Antibody values below the LLOQ were replaced by 0.5 × LLOQ. The 95% CI was calculated based on the t‐distribution of the log‐transformed values for GMC and GM levels, then back‐transformed to the original scale for presentation. CI, confidence interval; RBD_w, receptor‐binding domain (W subscript refers to the Wuhan‐Hu‐1 strain); S_1w, S_1w part of the spike protein (W subscript refers to the Wuhan‐Hu‐1 strain); sVNT_w, surrogate virus‐neutralizing test (W subscript refers to the Wuhan‐Hu‐1 strain).

FIGURE 3

Lentivirus pseudotyping neutralization test for Delta and Omicron BA.1 in a random subset of 14 baseline sera from each primary vaccine group (a). Results from the same individuals, 2 weeks after the SpikoGen® booster dose (b). Column height shows GMT

FIGURE 4

Lentivirus pseudotype viral neutralization test (pVNT) for each major variants of concern was performed on 42 trial subjects (14 per primary vaccine group). Baseline sera were tested for neutralization titres against Delta and Omicron. Individual titres and group GMT (top bar) for Day 14 post‐booster sera against each of the variants of concern are shown for the selected subjects (a). The fold‐change in pVNT for each variant was calculated by reference to the Alpha ancestral strain (b). The pVNT results against each variant for each individual subject are shown as a heatmap where the intensity of the shading reflects the level of the pVNT titre as shown by the colour scale on the right (c). Pairwise correlations were performed of pVNT results against each variant of concern for Day 14 post‐booster sera of 44 subjects and depicted as a heatmap with the correlations shown in each cell and colour scale depicting the extent of correlation shown on the right (all correlations shown were significant at p < 0.05 (d)

FIGURE 5

Solicited local and systemic adverse events. Shown is the percentage of participants in each group (SpikoGen®, placebo) with solicited local (upper figure) and systemic (lower figure) adverse events according to the toxicity grading scale during the 7 days after the booster. There were no grade 4 (life‐threatening) events

FIGURE 6

The trend of S_1w and RBD_w antibodies in primary vaccination and booster dose of SpikoGen®. RBD_w, receptor‐binding domain (W subscript refers to the Wuhan‐Hu‐1 strain); S_1w, S_1w part of the spike protein (W subscript refers to the Wuhan‐Hu‐1 strain).