Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial
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SciScore for 10.1101/2021.09.17.21263758: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Written informed consent was obtained from all participants.
IRB: This study was approved by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University (TMEC 21-005) and authorized by the Thailand Food and Drug Administration (FDA-21-018).Sex as a biological variable A negative urinary pregnancy test was required of women having reproductive capacity prior to administration of each study vaccine dose. Randomization Study design and participants: The phase 1 segment of a randomised, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University (Bangkok, Thailand). Blinding A protocol … SciScore for 10.1101/2021.09.17.21263758: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Written informed consent was obtained from all participants.
IRB: This study was approved by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University (TMEC 21-005) and authorized by the Thailand Food and Drug Administration (FDA-21-018).Sex as a biological variable A negative urinary pregnancy test was required of women having reproductive capacity prior to administration of each study vaccine dose. Randomization Study design and participants: The phase 1 segment of a randomised, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University (Bangkok, Thailand). Blinding A protocol safety review committee regularly reviewed blinded safety data; a Data Safety Monitoring Board monitored unblinded safety data and recommended two formulations for advancing to phase 2. Power Analysis The study was designed to have greater than 90% power to identify the candidate with the highest response as measured by the NT50 by ranked GMCs, assuming the true GMC is at least 1·5-fold larger than the second highest candidate group and to provide a preliminary safety evaluation of the candidates. Cell Line Authentication Authentication: We also calculated 80% neutralisation titres (NT80); nevertheless, as the PNA was not validated for this measurement, these results are not presented. Table 2: Resources
Antibodies Sentences Resources Healthy adults 18–59 years of age with body mass index 17 to 40 kg/m2,-negative hepatitis B surface antigen and SARS-CoV-2, HIV, and hepatitis C antibody tests were eligible to participate. SARS-CoV-2, HIVsuggested: NoneVaccine potency was measured by direct enzyme-linked immunosorbent assay (ELISA) using a human monoclonal antibody (CR30227) to SARS-CoV-2 spike glycoprotein S1 (LakePharma Inc) and an NDV-HXP-S standard that had been calibrated to a purified HXP-S reference8 by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) densitometry. CR30227suggested: NoneSARS-CoV-2 spike glycoprotein S1suggested: NoneAfter washing, horseradish peroxidase (HRP) enzyme-conjugated goat anti-human IgG-Fc (Jackson ImmunoResearch Laboratories) was added for 60 minutes at room temperature (15-30°C), then washed. anti-human IgG-Fcsuggested: NoneConcentrations were transformed to binding antibody units per mL (BAU/mL), based on the WHO International Standard for anti-SARS-CoV-2 immunoglobulin,9 using a conversion factor determined during assay validation (1/7·9815). anti-SARS-CoV-2suggested: NoneThe neutralising titre of a serum sample was calculated as the reciprocal serum dilution corresponding to the 50% neutralisation antibody titre (NT50) for that sample; the NT50 titres were transformed to international units per mL (IU/mL), based on the WHO international standard for anti-SARS-CoV-2 immunoglobulin, using a conversion factor determined during assay validation (1/1,872). anti-SARS-CoV-2 immunoglobulinsuggested: NoneAnti-human IFN-γ/IL-5 detection solution (containing anti-human IFN-γ fluorescein isothiocyanate [FITC] and anti-human IL-5 [biotin] detection antibodies) was then added to the wells and incubated at room temperature (15-30°C) for 2 h ± 10min to detect IFN-γ and IL-5 cytokine captured on the bottom of the well. Anti-human IFN-γ/IL-5suggested: Noneanti-human IFN-γsuggested: Noneanti-human IL-5suggested: NoneExperimental Models: Cell Lines Sentences Resources Serum-virus complexes were then transferred onto 96 well white flat-bottom plates (Corning), previously seeded overnight with Vero E6 cells (Nexelis) and incubated at 37°C and 5% CO2 for 20 ± 2 hours. Vero E6suggested: NoneThe assay’s LLOQ for IFN-γ was 109 SFU/106 cells and for IL-5 was 43 SFU/106 cells. SFU/106suggested: NoneSoftware and Algorithms Sentences Resources Bound secondary antibody was reacted with 3,3′,5,5′-tetramethylbenzidine (TMB) ELISA peroxidase substrate (Bio-Rad Laboratories) and incubated for 30 minutes at room temperature (15-30°C) before the reaction was stopped with 2N H2SO4. Bio-Rad Laboratoriessuggested: (Bio-Rad Laboratories, RRID:SCR_008426)All statistical analyses were performed by an independent statistician using SAS version 9·4. SASsuggested: (SASqPCR, RRID:SCR_003056)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:The study has several limitations. The sample size per treatment group was small, limiting precision, and assessments were restricted to 43 days for immunogenicity and 57 days for reactogenicity and safety, narrowing our perspective to acute outcomes only. These are inherent problems of phase 1 trials and interim analyses in a pandemic response setting. Nevertheless, as clinical trials with similar vaccines are underway in Vietnam (NCT04830800) and Brazil (NCT04993209), we determined that publication of early data is a priority. The study had strengths as well. The vaccine construct is a novel platform expressing a second-generation pre-fusion stabilized S protein in a membrane-bound trimeric conformation. We hypothesize that these characteristics contribute to the vaccine’s notable immunogenicity, even without the CpG1018 adjuvant. The anti-S ELISA and PNA used to assess vaccine-homologous NT50 potency were validated and results are expressed in International Units9 for future comparisons. The induction of anti-S binding and neutralising antibodies was contrasted with mean levels in human convalescent serum and found to be superior, especially in the mid- and high-dose groups. However, the neutralisation assay is not a live virus assay; therefore, it is presently uncertain how our functional antibody readouts can be used to benchmark against live virus neutralising antibody levels induced by authorized or licensed vaccines. Correlation between neutralising antibody titres an...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04764422 Recruiting Assess the Safety and Immunogenicity of NDV-HXP-S Vaccine in… NCT04830800 Recruiting A Phase 1/2 Safety and Immunogenicity Trial of COVID-19 Vacc… NCT04993209 Recruiting Clinical Trial of the COVID-19 Vaccine (Recombinant, Inactiv… 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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