Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19
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Abstract
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18–55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.
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SciScore for 10.1101/2020.11.04.20226282: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Healthy seronegative subjects 18-55 years of age who met all inclusion criteria and no exclusion criterion were enrolled and randomized into nine groups. Blinding The participants and the personnel collecting the safety information and testing laboratories remained blinded to treatment allocation. Power Analysis not detected. Sex as a biological variable Analysis Populations and Statistical Analysis Plan: Overall, 180 healthy SATRS-COV-2 seronegative male and female subjects 18 to 55 years of age were randomized in a 1:1:1:1:1:1:1:1:1 ratio into nine treatment groups. Table 2: Resources
No key resources detected.
Results from OddPub: We did …
SciScore for 10.1101/2020.11.04.20226282: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Healthy seronegative subjects 18-55 years of age who met all inclusion criteria and no exclusion criterion were enrolled and randomized into nine groups. Blinding The participants and the personnel collecting the safety information and testing laboratories remained blinded to treatment allocation. Power Analysis not detected. Sex as a biological variable Analysis Populations and Statistical Analysis Plan: Overall, 180 healthy SATRS-COV-2 seronegative male and female subjects 18 to 55 years of age were randomized in a 1:1:1:1:1:1:1:1:1 ratio into nine treatment groups. Table 2: Resources
No key resources detected.
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:Like any early-phase clinical trial, this study has several limitations beyond the obvious concern regarding small group size when testing multiple dose levels and formulations (n=20/group). For comparisons between formulations however, the small group risk was mitigated by the fact that results across the three CoVLP dose levels were highly consistent (n=60 for CoVLP alone or with each adjuvant). Another obvious concern is the relatively limited range of immune response parameters available at the time of writing. Although the data presented herein provide a ‘first look’ at the immune response induced by the different formulations, the immune profiles will be further investigated in the coming months. Finally, like all other early-phase trials, our study assessed only the short-term (day 42) response to vaccination and the durability of these responses will only become apparent as subjects are followed for longer periods of time. However, based on the robust high antibody and balanced cellular responses to the adjuvanted CoVLP formulations and our previous experience with plant-derived VLP vaccines targeting influenza, we anticipate that the CoVLP-induced responses are likely to last for at least 6 months30, 50. In conclusion, this first trial of CoVLP alone or adjuvanted with either CpG1018 or AS03 suggests that our plant-derived candidate vaccine is well-tolerated and immunogenic. Its immunogenicity, particularly at low doses, is dramatically enhanced by the presence of an...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04450004 Active, not recruiting Safety, Tolerability and Immunogenicinity of a Coronavirus-L… 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.
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