Comparative immunogenicity and safety of SpikoGen®, a recombinant SARS-CoV-2 spike protein vaccine in children and young adults: An immuno-bridging clinical trial.

BACKGROUND: SpikoGen® is a recombinant subunit spike protein ectodomain vaccine manufactured in insect cells and formulated with the novel polysaccharide-based Advax-CpG55.2 adjuvant. This study aimed to compare the immunogenicity and safety of SpikoGen® vaccine in children, adolescents and young adults. METHODS: This was a non-randomized, three-arm, open-label, parallel-group, immuno-bridging, non-inferiority trial to compare the immunogenicity and safety of a primary course of two intramuscular doses of SpikoGen® vaccine in children aged 5 to < 12 years, adolescents aged 12 to < 18 years and young adults aged 18 to 40 years. Children 5-12 years received a half dose of 12.5 µg spike protein, whereas the other groups received the full vaccine dose. Vaccine immunogenicity was evaluated via assessment of serum anti-spike and neutralizing antibodies 14 days after the second dose. Solicited adverse events were recorded for 7 days after each vaccination. Safety assessments including serious adverse events were continued through six months after the second dose in children and adolescents. RESULTS: Two weeks after the second dose, seroconversion rates for neutralizing antibody levels were not significantly different for children (59.50 %), adolescents (52.06 %) and adults (56.01 %). The 95 % confidence interval of the difference in seroconversion rates between children and adults was within the prespecified non-inferiority margin of 10 % (-12 % to 5 %). SpikoGen® vaccine was well tolerated in all age groups with the most common solicited adverse events being injection site pain and fatigue which were generally transient and mild. CONCLUSION: SpikoGen® vaccine was shown to be safe, well tolerated and immunogenic in children as young as 5 years of age, with non-inferior responses to those seen in adults. The Iranian FDA authorisation of SpikoGen® vaccine is now extended down to 5 years of age.

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.

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.

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.

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.

Evaluation of the Physicochemical and Biological Stability of Cetuximab under Various Stress Condition.

Cetuximab is a chimeric monoclonal antibody against epidermal growth factor receptor (EGFR) and it is approved for treatment of human colorectal cancer and squamous cell carcinoma of head and neck. The aim of this research was to study the stability of cetuximab finish product (5 mg/mL) under various stress conditions including mechanical, thermal, light stress, and various freeze-thaw cycles. To determine the effects of environmental stresses on the physicochemical properties and bioactivity of cetuximab, a combination of physicochemical and cell-based biological methods including size exclusion chromatography (SEC), cation exchange chromatography (CEX), flow cytometry-based binding assay, and MTS cell viability/proliferation assay was used. The results obtained by the SEC and CEX methods revealed that incubation of cetuximab at 25 and 30 °C, shaking, and various freeze-thaw cycles caused no physicochemical instability. However, functional analysis of the samples exposed to the above-mentioned conditions revealed a significant decrease in the bioactivity of cetuximab indicated by a significant reduction in the cell binding and growth inhibitory effects of cetuximab in EGFR overexpressing cancer cell line (A431). Incubation of cetuximab at 40 and 50 °C led to polymerization and fragmentation of the mAb and resulted in a significant decrease in the bioactivity of the mAb. Our findings show that the light exposure had the most destructive effects on physicochemical and biological characteristics of cetuximab. In conclusion, we found that all mentioned stress conditions significantly affect the bioactivity of cetuximab. Our finding highlights the importance of bioactivity evaluation of biopharmaceuticals in their quality control assessment.