A Phase1 Results of a Non-Stabilized Spike-Encoding mRNA Vaccine in Adults

  1. Sivaporn Gatechompol
  2. Wonngarm Kittanamongkolchai
  3. Chutitorn Ketloy
  4. Eakachai Prompetchara
  5. Arunee Thitithanyanont
  6. Anan Jongkaewwattana
  7. Supranee Buranapraditkun
  8. Mohamad-Gabriel Alameh
  9. Sasiwimol Ubolyam
  10. Jiratchaya Sophonphan
  11. Tanakorn Apornpong
  12. Stephen Kerr
  13. Adeeba Kamarulzaman
  14. Sarawut Siwamogsatham
  15. Eugène Kroon
  16. Thanyawee Puthanakit
  17. Kanitha Patarakul
  18. Tanapat Palaga
  19. Wassana Wijagkanalan
  20. Drew Weissman
  21. Kiat Ruxrungtham
  22. ChulaVAC-001 study team

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Abstract

Background

Effective COVID-19 mRNA vaccines are mainly available in high-income countries. ChulaCov19, a prefusion non-stabilized Spike protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine development, aims to enhance accessibility of mRNA vaccine and future pandemic preparedness for low- to middle-income countries.

Methods

Seventy-two eligible volunteers, 36 aged 18-55 (adults) followed by 36 aged 56-75 (elderly) enrolled in a dose escalation study of ChulaCov19 mRNA vaccine. Two doses of vaccine were given 21 days apart at 10, 25, or 50 µg/dose (12/group). Safety was the primary and immunogenicity the secondary outcome. Human convalescents’ (HCS) and Pfizer/BioNTech vaccinees’ sera provided comparison panels.

Results

All three doses of ChulaCov19 were well tolerated and elicited robust dose-dependent and age- dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue, and headache were more common after the second dose. Four weeks after the second ChulaCov19: dose at 10, 25, and 50 µg dose, MicroVNT-50 Geometric mean titer (GMT) against wild-type was 848, 736 and 1,140 IU/mL, respectively, versus 267 IU/mL for HCS. All dose levels elicited 100% seroconversion, with GMT ratio 4-8-fold higher than for HCS (p<0.01), and high IFNγ spot-forming cells/million peripheral blood mononuclear cells. The 50 µg dose induced better cross-neutralization against Alpha, Beta, Gamma, and Delta variants than lower doses.

Conclusions

ChulaCov19 at 50 µg/dose is well tolerated and elicited higher neutralizing antibodies than HCS with strong T-cell responses. These antibodies cross neutralized four variants of concern and ChulaCov19 has therefore proceeded to phase 2 and 3 clinical trials.

Trial registration number

ClinicalTrials.gov Identifier NCT04566276

Graphical Abstract

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  1. ScreenIT

    SciScore for 10.1101/2022.05.12.22274989: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The trial and the Investigational New Drug application were approved by the ethics committee of the Faculty of Medicine, Chulalongkorn University, Bangkok, and Thailand’s Food and Drug Administration, respectively.
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis was conducted with Stata 15 (Statacorp LLC, College Station, TX, USA).
    Statacorp
    suggested: None

    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 limitations of this study include: the sample size is small due to the phase 1 uncontrolled dose-finding design. The exploratory comparative immunogenicity analyses with convalescent sera or Pfizer/BNT vaccinees’ sera are not direct head-to-head comparisons and can contain bias. Convalescent sera were collected during the rise of the Delta variant outbreak, and possibly antibody responses are stronger against Delta than WT. To minimize bias, the convalescent and Pfizer/BNT vaccinees’ serum samples were tested at the same laboratories together with the ChulaCov19 vaccinated samples. In addition, a RCT phase 2 study has commenced and a larger scale immune-bridging, non-inferiority phase 3 study is planned. In summary, ChulaCov19 mRNA vaccine is well tolerated and elicited strong SARS-CoV2 specific B- and T-cell immunogenicity and is currently under Phase 2 and later clinical development.

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

    IdentifierStatusTitle
    NCT04566276Active, not recruitingChulaCov19 Vaccine in Healthy Adults

    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.

  2. Version published to 10.1101/2022.05.12.22274989v1 on medRxiv