Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in adolescents in Taiwan: A double-blind, randomized, placebo-controlled phase 2 trial
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Abstract
Background
MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on the prefusion spike protein S-2P and adjuvanted with CpG 1018 and aluminum hydroxide. Although MVC-COV1901 has been licensed for emergency use for adults in Taiwan, the safety and immunogenicity of MVC-COV1901 in adolescents remained unknown. As young people play an important role in SARS-CoV-2 transmission and epidemiology, a vaccine approved for adolescents and eventually, children, will be important in mitigating the COVID-19 pandemic.
Methods
This study is a prospective, double-blind, multi-center phase 2 trial evaluating the safety, tolerability and immunogenicity of two doses of the SARS-CoV-2 vaccine MVC-COV1901 in adolescents. Healthy adolescents from age of 12 to 17 years were recruited and randomly assigned (6:1) to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. The primary outcomes were safety and immunogenicity from the day of first vaccination (Day 1) to 28 days after the second vaccination (Day 57), and immunogenicity of MVC COV1901 in adolescents as compared to young adult vaccinees in terms of neutralizing antibody titers and seroconversion rate. The secondary outcomes were safety and immunogenicity of MVC-COV1901 as compared to placebo in adolescents in terms of immunoglobulin titers and neutralizing antibody titers over the study period.
Results
Between July 21, 2021 and December 22, 2021, a total of 399 adolescent participants were included for safety evaluation after enrollment to receive at least one dose of either MVC-COV1901 (N=341) or placebo (N=58). Of these, 334 and 46 participants went on to receive two doses of either MVC-COV1901 or placebo, respectively, and were included in the per protocol set (PPS) for immunogenicity analysis. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups. The most commonly reported adverse events were pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups.
Conclusions
The safety and immunogenicity data presented here showed that MVC-COV1901 has similar safety profile and non-inferior immunogenicity in adolescents compared to young adults.
ClinicalTrials.gov registration
NCT04951388.
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SciScore for 10.1101/2022.03.14.22272325: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Finally, participant and/or the participant’s legal representative must have provided written informed consent.
IRB: The trial protocol and informed consent form were approved by Taiwan Food and Drug Administration (TFDA) and the ethics committees at the conducting sites: Mackay Memorial Hospital Hsinchu (Hsinchu City), Chang-Gung Memorial Hospital Linkou (New Taipei City), Mackay Memorial Hospital (Taipei City), National Taiwan University Hospital Hsinchu (Hsinchu City), and National Taiwan University Hospital (Taipei City).Sex as a biological variable Additional criteria applied to females only: negative pregnancy test, non-childbearing potential or, if with childbearing … SciScore for 10.1101/2022.03.14.22272325: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Finally, participant and/or the participant’s legal representative must have provided written informed consent.
IRB: The trial protocol and informed consent form were approved by Taiwan Food and Drug Administration (TFDA) and the ethics committees at the conducting sites: Mackay Memorial Hospital Hsinchu (Hsinchu City), Chang-Gung Memorial Hospital Linkou (New Taipei City), Mackay Memorial Hospital (Taipei City), National Taiwan University Hospital Hsinchu (Hsinchu City), and National Taiwan University Hospital (Taipei City).Sex as a biological variable Additional criteria applied to females only: negative pregnancy test, non-childbearing potential or, if with childbearing potential, abstinence or agreement to use medically effective contraception from 14 days before screening to 30 days following the last injection of study intervention. Randomization Eligible participants were those aged 12 (inclusive) to 17 (not legible if the participant turned 18 years old) at the time of randomization, with body mass index (BMI) at or above the third percentile according to World Health Organization (WHO) at the screening visit, and lack of travel within 14 days of screening and lack of any oversea travelling throughout the study period. Blinding Randomization and blinding: All eligible participants were randomized to receive either MVC-COV1901 or placebo in a 6:1 ratio. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources For secondary immunogenicity outcomes, comparisons of MVC-COV1901 against placebo were performed by measuring and expressing antigen-specific immunoglobulin titers and neutralizing antibody titers in samples taken at Visit 4 (28 days after the first dose of study intervention), Visit 6 (28 days after the second dose of study intervention), Visit 8 (90 days after the second dose of study intervention) and Visit 9 (209 days after the second dose of study intervention). antigen-specific immunoglobulinsuggested: NoneImmunogenicity was analyzed with the per protocol set (PPS) population, which consisted of the individuals who received the planned doses of randomized study intervention per schedule, were seronegative at baseline (neutralizing antibody titer < lower limit of detection at Visit 2), anti-N antibodies negative at Visit 2 and Visit 6, and did not have a major protocol deviations that were judged to impact the critical or key study data. anti-Nsuggested: NoneExperimental Models: Cell Lines Sentences Resources The serum-virus mixture was incubated and then added to the plates containing Vero E6 cells, followed by further incubation. Vero E6suggested: RRID:CVCL_XD71)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations apply to this study. The main limitation is that as this is a phase 2 study where efficacy was not assessed directly, but can only be inferred by established correlates of protection against SARS-CoV-2 [21, 22]. The data presented here make the case for further clinical assessment. Secondly, even though most safety events were grade 1, a small number of grade 3 events were observed that need to be evaluated in a greater study population. Notably, though, no grade 4 events were observed and there were also no cases of AESI and VAED. Other limitations relate to questions regarding the evolution of COVID-19 over the last year that clinical trials are in the process of catching up with. These questions include the duration of the antiviral response over several months after the second dose, the suitability of any given vaccine for current and future virus variants and if there is any additional protection afforded by booster shots. As Taiwan has started administering booster doses for adults including MVC-COV1901, future studies will investigate the suitability of MVC-COV1901 as homologous or heterologous booster after primary vaccination of adolescents.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04951388 Active, not recruiting A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in … Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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