Open label phase I/II clinical trial and predicted efficacy of SARS-CoV-2 RBD protein vaccines SOBERANA 02 and SOBERANA Plus in children

  1. Rinaldo Puga-Gómez
  2. Yariset Ricardo-Delgado
  3. Chaumey Rojas-Iriarte
  4. Leyanis Céspedes-Henriquez
  5. Misleidys Piedra-Bello
  6. Dania Vega-Mendoza
  7. Noelvia Pestana Pérez
  8. Beatriz Paredes-Moreno
  9. Meiby Rodríguez-González
  10. Carmen Valenzuela-Silva
  11. Belinda Sánchez-Ramírez
  12. Laura Rodríguez-Noda
  13. Rocmira Pérez-Nicado
  14. Raul González-Mugica
  15. Tays Hernández-García
  16. Talía Fundora-Barrios
  17. Martha Dubet Echevarría
  18. Juliet María Enriquez-Puertas
  19. Yenicet Infante Hernández
  20. Ariel Palenzuela-Díaz
  21. Evelyn Gato-Orozco
  22. Yanet Chappi-Estévez
  23. Julio Cesar Francisco-Pérez
  24. Miladi Suarez Martinez
  25. Ismavy C. Castillo-Quintana
  26. Sonsire Fernandez-Castillo
  27. Yanet Climent-Ruiz
  28. Darielys Santana-Mederos
  29. Yanelda García-Vega
  30. María Eugenia Toledo-Romani
  31. Delaram Doroud
  32. Alireza Biglari
  33. Yury Valdés-Balbín
  34. Dagmar García-Rivera
  35. Vicente Vérez-Bencomo
  36. SOBERANA Research Group

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Abstract

Objectives

To evaluate heterologous vaccination scheme in children 3-18 y/o combining two SARS-CoV-2 r-RBD protein vaccines.

Methods

A phase I/II open-label, adaptive and multicenter trial evaluated the safety and immunogenicity of two doses of SOBERANA02 and a heterologous third dose of SOBERANA Plus in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (in phase I) and safety/immunogenicity (in phase II) measured by anti-RBD IgG ELISA, molecular and live-virus neutralization titers and specific T-cells response. A comparison with adult‘s immunogenicity and prediction of efficacy were done based on immunological results

Results

Local pain was the unique adverse event with frequency >10%, none was serious or severe. Two doses of SOBERANA 02 elicited humoral immune response similar to natural infection; the third dose increased significantly the response in all children, similar to that achieved in vaccinated young adults and higher than in convalescents children. The neutralizing titer was evaluated in a participant‘s subset: GMT was 173.8 (CI 95% 131.7; 229.5) vs. alpha, 142 (CI 95% 101.3; 198.9) vs. delta and 24.8 (CI 95% 16.8; 36.6) vs. beta. An efficacy > 90% was estimated.

Conclusion

The heterologous scheme was safe and immunogenic in children 3-18 y/o. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000374

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  1. Version published to 10.1101/2022.03.03.22271313v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2022.03.03.22271313: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical issues: The trial was approved by the Ethical Committee at the “Juan Manuel Marquez” Pediatric Hospital and endorsed by the Cuban National Pediatric Group.
    Consent: Written informed consent was obtained from both parents; children ≥over 12 y/o should assent.
    Sex as a biological variablenot detected.
    RandomizationPeripheral blood mononuclear cells were obtained before vaccination and after the third dose (day 70) in a participants’ subset of 45 children randomly selected in each age subgroup.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Immunogenicity assessment: A quantitative ultramicro ELISA (UMELISA SARS-CoV-2 anti-RBD, Centre for Immunoassay, Havana, Cuba) determined the concentration of anti-RBD IgG antibodies in sera, expressed as AU/mL.
    anti-RBD
    suggested: None
    anti-RBD IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Clinical sites were certified by the National Immunization Program.
    National Immunization Program
    suggested: (Centers for Disease Control and Prevention, RRID:SCR_012976)

    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

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  3. Version published to 10.1101/2022.03.03.22271313v1 on medRxiv