Safety and immunogenicity of anti-SARS CoV-2 conjugate vaccine SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults: Phase IIb Clinical Trial

  1. María Eugenia Toledo-Romani
  2. Mayra García-Carmenate
  3. Leslyhana Verdecia-Sánchez
  4. Suzel Pérez-Rodríguez
  5. Meybis Rodriguez-González
  6. Carmen Valenzuela-Silva
  7. Beatriz Paredes-Moreno
  8. Belinda Sanchez-Ramirez
  9. Raúl González-Mugica
  10. Tays Hernández-Garcia
  11. Ivette Orosa-Vázquez
  12. Marianniz Díaz-Hernández
  13. María Teresa Pérez-Guevara
  14. Juliet Enriquez-Puertas
  15. Enrique Noa-Romero
  16. Ariel Palenzuela-Diaz
  17. Gerardo Baro-Roman
  18. Ivis Mendoza-Hernández
  19. Yaima Muñoz
  20. Yanet Gómez-Maceo
  21. Bertha Leysi Santos-Vega
  22. Sonsire Fernandez-Castillo
  23. Yanet Climent-Ruiz
  24. Laura Rodríguez-Noda
  25. Darielys Santana-Mederos
  26. Yanelda García-Vega
  27. Guang Wu-Chen
  28. Delaram Doroud
  29. Alireza Biglari
  30. Tammy Boggiano-Ayo
  31. Yury Valdés-Balbín
  32. Daniel García-Rivera
  33. Dagmar García-Rivera
  34. Vicente Vérez-Bencomo
  35. SOBERANA Research Group

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Abstract

Background

We report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults in a phase IIb clinical trial.

Method

This phase IIb trial was designed as parallel, multicentre, adaptive, double blind, randomized and placebo-controlled. Subjects (N=810) aged 19-80 years were randomized to receive two doses of the recombinant SARS CoV-2 receptor binding domain (RBD) conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredient of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD IgG concentration. Secondary outcomes were safety, reactogenicity and neutralizing antibodies.

Results

Seroconversion rate in vaccinees was respectively 76.3 and 96.8% after two or three doses, compared with 7.3% in placebo group. Anti-RBD IgG increased significantly after first and second dose of SOBERANA 02 respect to placebo group; and the third dose with SOBERANA Plus boosts the response compared to the second dose. Neutralizing IgG antibodies were detected against D614G and VOCs α, β and δ. Specific and functional antibodies were detected at least until 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%); with only one serious AE consistent with vaccination. Local pain was the most frequent AE.

Conclusions

Two doses of SOBERANA 02 were well tolerated, safe an immunogenic in adults aged 19-80 years old. The heterologous combination with a third dose of SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after finishing the vaccination schedule.

Trial registry

https://rpcec.sld.cu/trials/RPCEC00000347

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  1. ScreenIT

    SciScore for 10.1101/2022.01.01.21268271: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical considerations: The phase II clinical trial protocol was reviewed and approved by an ad hoc centralized Research Ethics Committee from the Medical Sciences University, Faculty of Medicine “Manuel Fajardo”, Havana, designed by the Health Innovation Committee from the Cuban Ministry of Health (MINSAP).
    Consent: Written informed consent was obtained from all participants.
    Sex as a biological variableHealthy adults aged 19-80 years, of both sexes were recruited through public advertisement at community or professional environment close to the clinical site.
    RandomizationParticipants and study design: Phase IIb was designed as a multicenter, adaptive, parallel, double blind, randomized, placebo controlled trial for evaluating the immunogenicity, safety and reactogenicity of two doses of SOBERANA 02 and the heterologous scheme with a third dose with SOBERANA Plus.
    BlindingParticipants and study design: Phase IIb was designed as a multicenter, adaptive, parallel, double blind, randomized, placebo controlled trial for evaluating the immunogenicity, safety and reactogenicity of two doses of SOBERANA 02 and the heterologous scheme with a third dose with SOBERANA Plus.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We calculated seroconversion rate for anti-RBD IgG antibodies (≥4-fold increase in antibody concentration over baseline) for each subject.
    anti-RBD IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    ) Products under evaluation: SOBERANA 02 (FINLAY-FR-2) and SOBERANA Plus (FINLAY-FR-1A) are vaccine candidates based on the recombinant receptor binding domain (RBD) of SARS-CoV-2 virus produced in CHO cells.
    CHO
    suggested: CLS Cat# 603479/p746_CHO, RRID:CVCL_0213)
    Software and Algorithms
    SentencesResources
    Platform: https://rpcec.sld.cu/trials/RPCEC00000347
    Platform
    suggested: (TRIO Platform, RRID:SCR_021596)
    The trial was conducted following the Declaration of Helsinki, Good Clinical Practice and the rules of the Cuban National Immunization Program.
    National Immunization Program
    suggested: (Centers for Disease Control and Prevention, RRID:SCR_012976)
    Statistical analyses were done using SPSS version 25.0; EPIDAT version 12.0 and Prism GraphPad version 6·0.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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 10.1101/2022.01.01.21268271v1 on medRxiv