Safety and immunogenicity of an egg-based inactivated Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomized, placebo-controlled, phase 1/2 trial in Vietnam

  1. Anh Duc Dang
  2. Thiem Dinh Vu
  3. Ha Hai Vu
  4. Van Thanh Ta
  5. Anh Thi Van Pham
  6. Mai Thi Ngoc Dang
  7. Be Van Le
  8. Thai Huu Duong
  9. Duoc Van Nguyen
  10. Saranath Lawpoolsri
  11. Pailinrut Chinwangso
  12. Jason S. McLellan
  13. Ching-Lin Hsieh
  14. Adolfo Garcia-Sastre
  15. Peter Palese
  16. Weina Sun
  17. Jose L. Martinez
  18. Irene Gonzalez-Dominguez
  19. Stefan Slamanig
  20. Juan Manuel Carreño
  21. Johnstone Tcheou
  22. Florian Krammer
  23. Ariel Raskin
  24. Huong Minh Vu
  25. Thang Cong Tran
  26. Huong Mai Nguyen
  27. Laina D. Mercer
  28. Rama Raghunandan
  29. Manjari Lal
  30. Jessica A. White
  31. Richard Hjorth
  32. Bruce L. Innis
  33. Rami Scharf

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Abstract

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  1. Version published to 10.1016/j.vaccine.2022.04.078
  2. ScreenIT

    SciScore for 10.1101/2022.02.01.22270253: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from all participants.
    IRB: This study was jointly approved by the Institutional Review Board of the Vietnam National Institute of Hygiene and Epidemiology as well as the Independent Ethics Committee of the Vietnam Ministry of Health (Approval Ref: 24/CN-HDDD dated 23 February, 2021) and authorized by the Vietnam Ministry of Health (Authorization reference: 1407/QD-BYT dated 26 February, 2021).
    Sex as a biological variableA negative urinary pregnancy test was required of women having reproductive capacity prior to administration of each study vaccine dose.
    RandomizationStudy design and participants: The phase 1 portion of a phase 1/2 randomized, observer-blind, placebo-controlled trial was conducted at Hanoi Medical University (Hanoi, Vietnam).
    BlindingA PSRT regularly reviewed blinded safety data.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Vaccine potency (i.e., amount of HXP-S antigen per dose) was measured by direct enzyme-linked immunosorbent assay (ELISA) using a human monoclonal antibody (CR3022) (8).
    CR3022
    suggested: None
    After 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-Fc
    suggested: None
    The neutralizing titre of a serum sample was calculated as the reciprocal serum dilution corresponding to the 50% neutralization 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 immunoglobulin
    suggested: None
    Cells were permeabilized and stained using the anti-nucleoprotein antibody 1C7C7 as previously described in detail (12) (13, 14).
    anti-nucleoprotein
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Vero E6 cells were seeded onto 96-well cell culture plates (20,000 cells/well) one day prior to the assay.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Bound secondary antibody was reacted with 3,3′,5,5′-tetramethylbenzidine 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 Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Serial dilutions of sera were prepared in 1X minimal essential medium (MEM; Life Technologies) at a starting dilution of 1:10.
    MEM
    suggested: (E-mem, RRID:SCR_016081)

    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. Also, 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, since clinical trials with similar vaccines are underway in Thailand (NCT04764422) and Brazil (NCT04993209), we determined that publication of early data is a priority, with a follow-on publication of the results of the full study. One additional weakness is the absence of Omicron (B.1.1.529) neutralization data, which was not generated for this initial study. The study had strengths as well. The vaccine construct is a novel platform expressing a second-generation prefusion-stabilized S protein in a membrane-bound trimeric conformation. We hypothesize that these characteristics contribute to the vaccine ‘s 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 units (9) for future comparisons. The induction of anti-S binding and neutralizing antibodies was contrasted with mean levels in human convalescent serum and found to be superior, especially in the mid- and high-dose groups. Furthermore, we have shown with a live neutralization assay that the vaccine candidate elicits neutralizing ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04830800RecruitingA Phase 1/2 Safety and Immunogenicity Trial of COVID-19 Vacc…
    NCT04764422RecruitingAssess the Safety and Immunogenicity of NDV-HXP-S Vaccine in…
    NCT04993209RecruitingClinical 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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2022.02.01.22270253 on medRxiv