A Phase I, Prospective, Randomized, Open-Labeled Study to Evaluate the Safety, Tolerability, and Immunogenicity of Booster Dose with MVC-COV1901 or MVC-COV1901(Beta) SARS-CoV-2 Vaccine in Adults

Background: The use of variant-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as a booster is being evaluated to overcome reduced neutralisation of variants induced by the original SARS-CoV-2 vaccine and waning protection over time.Methods: This is a phase one, prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901 or its Beta version, MVC-COV1901-Beta. One hundred and seven participants aged ≥18 and <55 years, who received two or three prior doses of MVC-COV1901 vaccines, were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg or 25 mcg of MVC-COV1901-Beta in a 1:1:1 ratio. The primary endpoints were the incidences of adverse events and immunogenicity of the booster dose from Visit 2 (the day of the booster) to Visit 5 (four weeks after the booster). Cellular immunity was also investigated with memory B cell (MBC) and T cell assays.Findings: Adverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 exhibited numerically higher levels of neutralising antibodies against ancestral SARS-CoV-2, Beta, and Omicron variant than participants with three prior doses of MVC-COV1901 regardless of the type of booster used. However, compared to 15 mcg of MVC-COV1901, 25 mcg of MVC-COV1901-Beta significantly improved neutralising antibody titre against Beta and Omicron (BA∙1) variant live virus, and BA∙4/BA∙5 pseudovirus. The booster dose also significantly increased the proportion of spike-specific MBCs, including those of the Beta and Omicron variants.Interpretation: MVC-COV1901-Beta can be effectively used as a booster dose against SARS-CoV-2, including the circulating BA∙4/BA∙5 Omicron variants.Trial Registration Details: This trial was registered at ClinicalTrials.gov: NCT05216601.Funding Information: Medigen Vaccine Biologics Corporation.Declaration of Interests: C. E. L., L. T.-C.- L., C.-C. W., W.-H. T., W.-C. L., and C. C. are employees of Medigen Vaccine Biologics Corporation. M.-C. L., N.-C. W., and K.-Y. A. H. declared no conflict of interest.Ethics Approval Statement: The trial protocol and informed consent form were approved by the Taiwan Food and Drug Administration and the institutional review boards of the Taipei Medical University Hospital (Taipei, Taiwan) and the Tri-Service General Hospital (Taipei, Taiwan). The trial was conducted in compliance with the principles of the Declaration of Helsinki and Good Clinical Practice. Safety data was monitored by an independent data and safety monitoring board (DSMB).