Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan

Abstract

Background MVC-COV1901, a recombinant protein vaccine containing pre-fusion-stabilised spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide, has been shown to be well tolerated with a good safety profile in healthy adults aged 20–49 years in a phase 1 trial, and provided a good cellular and humoral immune responses. We present the interim safety, tolerability, and immunogenicity results of a phase 2 clinical trial of the MVC-COV1901 vaccine in Taiwan. Methods This is a large-scale, double-blind, randomised, placebo-controlled phase 2 trial done at ten medical centres and one regional hospital in Taiwan. Individuals aged 20 years or older who were generally healthy or had stable pre-existing medical conditions were eligible for enrolment. Exclusion criteria included (but were not limited to) travel overseas within 14 days of screening, intention to travel overseas within 6 months of the screening visit, and the absence of prespecified medical conditions, including immunosuppressive illness, a history of autoimmune disease, malignancy with risk to recur, a bleeding disorder, uncontrolled HIV infection, uncontrolled hepatitis B and C virus infections, SARS-CoV-1 or SARS-CoV-2 infections, an allergy to any vaccine, or a serious medical condition that could interfere with the study. Study participants were randomly assigned (6:1) to receive two doses of either MVC-COV1901 or placebo, administered via intramuscular injection on day 1 and day 29. MVC-COV1901 contained 15 μg of S-2P protein adjuvanted with 750 μg CpG 1018 and 375 μg aluminium hydroxide in a 0·5 mL aqueous solution, and the placebo contained the same volume of saline. Randomisation was done centrally by use of an interactive web response system, stratified by age (≥20 to <65 years and ≥65 years). Participants and investigators were masked to group assignment. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from day 1 (the day of the first dose) to day 57 (28 days after the second dose). Safety was assessed in all participants who received at least one dose. Immunogenicity was assessed by measuring geometric mean titres (GMTs) and seroconversion rates of neutralising antibody and antigen-specific IgG in the per-protocol population. This study is registered with ClinicalTrials.gov , NCT04695652 . Findings Of 4173 individuals screened between Dec 30, 2020, and April 2, 2021, 3854 were enrolled and randomly assigned: 3304 to the MVC-COV1901 group and 550 to the placebo group. A total of 3844 participants (3295 in the MVC-COV1901 group and 549 in the placebo group) were included in the safety analysis set, and 1053 participants (903 and 150) had received both doses and were included in the per-protocol immunogenicity analysis set. From the start of this phase 2 trial to the time of interim analysis, no vaccine-related serious adverse events were recorded. The most com...

The reactogenicity and immunogenicity of a booster dose after the second dose of a protein subunit vaccine MVC-COV1901: An extension to an open-label, dose-escalation, and non-randomized phase 1 study

“…Anti-SARS-CoV-2 spike antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) using customized 96-well plates coated with S-2P antigen and expressioned in Binding Antibody Unit per mL (BAU/mL) [7]. Neutralizing antibody levels were measured by live-SARS-CoV-2 (Wuhan wildtype, hCoV-19/Taiwan/4/2020, GISAID# EPI_ISL_411927) neutralization assay previously performed [6]. Briefly, two-fold serial dilutions of serum samples were mixed with equal volume of 100 TCID 50 /50 μL of virus and incubated at 37 °C for one hour.…”

“…After incubation, the mixture was added to Vero E6 cells and incubated at 37 °C for four to five days. The results were expressed in WHO Standardized International Unit per mL (IU/mL, WHO Standardized) according to previously established methods [6]…”

“…Boosting with same type of vaccine (homologous) or different type of vaccine (heterologous) to the primary series of vaccination has shown to be effective in enhance immunogenicity against VoCs [3][4][5]. MVC-COV1901 is a protein subunit COVID-19 vaccine based on the stable prefusion spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide that has been authorized for emergency use in Taiwan [6]. The phase 1 clinical trial of MVC-COV1901 was designed as a dose-escalation trial with three groups of dose levels at 15 subjects for each group [7].…”

“…Introduction: MVC-COV1901 is a protein subunit COVID-19 vaccine based on the stable prefusion spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide. Interim results of phase 2 clinical trial demonstrated favorable reactogenicity and immunogenicity and the vaccine has been authorized for use in Taiwan since August 2021 [1]. However, the antibody persistence after the second dose and the effects of a booster dose remained unknown at the time.…”

“…MD was used as the booster dose for the LD and MD group, while HD was used for the HD group. Antibody level was measured on day 209 by enzyme-linked immunosorbent assay (ELISA) against SARS-CoV-2 spike protein, and by live-virus SARS-CoV-2 neutralization assay [1], with NT 50 GMTs expressed as neutralization titer.…”