Safety and Immunogenicity of CpG 1018 and Aluminium Hydroxide-Adjuvanted SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901: A Large-Scale Double-Blinded, Randomised, Placebo-Controlled Phase 2 Trial

Hsieh, S.-M.; Liu, M.-C.; Chen, Y.-H.; Lee, W.-S.; Hwang, S.-J.; Cheng, S.-H.; Ko, W.-C.; Hwang, K.-P.; Wang, N.-C.; Lee, Y.-L.; Lin, Y.-L.; Shih, S.-R.; Huang, C.-G.; Liao, C.-C.; Liang, J.-J.; Chang, C.-S.; Chen, C.; Lien, C. E.; Tai, I.-C.; Lin, T.-Y.

Background We have assessed the safety and immunogenicity of MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide against COVID-19. Methods This is a phase 2, prospective, double-blinded, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of [≥] 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 mcg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652. Findings From the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) was recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662.3 (408 IU/mL), the GMT ratio was 163.2, and the seroconversion rate was 99.8%. Interpretation MVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials, and could enable regulatory considerations for Emergency Use Authorisation (EUA). Funding Medigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.