ABSTRACT
Older adults are subject to higher COVID-19 infection and mortality rates. Even though vaccination programs prioritize the elderly, they are under-represented in clinical trials. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine has been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age. To further assess safety and immunogenicity of MVC-COV1901 vaccine in participants of 65 years and older, a double-blind, randomized, multi-center study compared high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart. The results have been stratified by the comorbidity status. Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities. Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommended high dose for the elderly.
Subject(s)
COVID-19ABSTRACT
Background: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018.Methods: 45 healthy adults from 20 to 49 years of age were to be administered two vaccinations of MVC-COV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second vaccination at the time of the interim analysis. Adverse events (AEs) and laboratory data were recorded for the safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays, SARS-CoV-2 spike-specific immunoglobulin G (IgG), and cellular immune response at various time points.Findings: Solicited adverse events were mostly mild and similar in all three dose groups. No subject experienced fever. After the second vaccination, serum neutralizing activity for wild-type virus was detected in all participants of the 15 μg and 25 μg dose groups with geometric mean values (76•3 [95% CI: 53•75 ~108•33], and 167•4 [95% CI: 122.05 ~229.61]) 1•8 to 3•9 times those of a panel of control convalescent serum specimens (42•7, [95%CI: 26•38~69•04]). The cellular immune response induced by MVC-COV1901 demonstrated substantially higher numbers of IFN-γ- than IL-4- producing cells in human peripheral blood mononuclear cells, suggesting a Th1-skewed immune response.Interpretation: The MVC-COV1901 vaccine was well tolerated and elicited robust immune responses especially in the 15 μg and 25 μg dose groups and is suitable for further development.Trial Registration: ClinicalTrials.gov NCT 04487210Funding: Medigen Vaccine Biologics Corporation.Conflict of Interest: Szu-Min Hsieh, Shan-Chwen Chang, Wang-Da Liu, Yu-Shan Huang declared that they have no knowncompeting financial interests or personal relationships that could have appeared to influence the work reported in this paper; Yi-Jiun Lin, Erh-Fang Hsieh, Wei-Cheng Lian, Charles Chen, I-Chen Tai are employee ofMedigen Vaccine Biologics Corporation and reported grants from Taiwan Centers for Disease Control, Ministry of Health and Welfare, during the conduct of the study. In addition, Yi-Jiun. Lin and Charles Chen have a patent US63/040,696 pending. Robert Janssen is an employee of Dynavax Technologies Corporation.Ethical Approval: The trial protocol and informed consent form were approved by the Taiwan Food and Drug Administration and the ethics committee at the site. The trial was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. An independent data and safety monitoring board (DSMB) was established to monitor safety data and the trial conduct.