An inactivated SARS-CoV-2 vaccine is safe and induces humoral and cellular immunity against virus variants in healthy children and adolescents in Chile

  1. Jorge A Soto
  2. Felipe Melo-González
  3. Cristián Gutierrez-Vera
  4. Bárbara M Schultz
  5. Roslye V Berríos-Rojas
  6. Daniela Rivera-Pérez
  7. Alejandro Piña-Iturbe
  8. Guillermo Hoppe-Elsholz
  9. Luisa F Duarte
  10. Yaneisi Vázquez
  11. Daniela Moreno-Tapia
  12. Mariana Ríos
  13. Pablo A Palacios
  14. Richard Garcia-Betancourt
  15. Álvaro Santibañez
  16. Constanza Mendez
  17. Benjamín Diethelm-Varela
  18. Patricio Astudillo
  19. Mario Calvo
  20. Antonio Cárdenas
  21. Marcela González
  22. Macarena Goldsack
  23. Valentina Gutiérrez
  24. Marcela Potin
  25. Andrea Schilling
  26. Lorena I Tapia
  27. Loreto Twele
  28. Rodolfo Villena
  29. Alba Grifoni
  30. Alessandro Sette
  31. Daniela Weiskopf
  32. Rodrigo A Fasce
  33. Jorge Fernández
  34. Judith Mora
  35. Eugenio Ramírez
  36. Aracelly Gaete-Argel
  37. Mónica Acevedo
  38. Fernando Valiente-Echeverría
  39. Ricardo Soto-Rifo
  40. Angello Retamal-Díaz
  41. Nathalia Muñoz-Jofré
  42. PedCoronaVac03CL Study Group
  43. Xing Meng
  44. Qianqian Xin
  45. Eduardo Alarcón-Bustamante
  46. José V González-Aramundiz
  47. Nicole Le Corre
  48. María Javiera Álvarez
  49. Pablo A González
  50. Katia Abarca
  51. Cecilia Perret
  52. Leandro J Carreño
  53. Alexis M Kalergis
  54. Susan M Bueno

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Abstract

Background

Multiple vaccines against SARS-CoV-2 have been evaluated in clinical trials, but very few include the pediatric population. The inactivated vaccine CoronaVac ® has shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. This study is an interim safety and immunogenicity report of a phase 3 clinical trial for CoronaVac ® in healthy children and adolescents in Chile.

Methods

Participants aged 3 to 17 years old received two doses of CoronaVac ® in a four-week interval. Local and systemic adverse reactions were registered in 699 participants that received the first dose and 381 that received the second dose until December 31 st , 2021. Whole blood samples were collected from 148 participants for humoral and cellular immunity analyses.

Results

The primary adverse reaction reported after the first and second dose was pain at the injection site. The adverse reactions observed were primarily mild and local, and no severe adverse events were reported. Four weeks after the second dose, a significant increase in the levels of total and neutralizing antibodies was observed. Increased activation of specific CD4 + T cells was also observed four weeks after the second dose. Although antibodies induced by vaccination neutralize variants Delta and Omicron, titers were lower than the D614G variant. Importantly, comparable T cell responses were detected against these variants of concern.

Conclusions

CoronaVac ® is safe and immunogenic in subjects aged 3-17 years old and is thus likely to confer protection against infection caused by SARS-CoV-2 variants in this target population.

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  1. ScreenIT

    SciScore for 10.1101/2022.02.15.22270973: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: This trial was approved by each Institutional Ethical Committee (ID 210616012) and the Chilean Public Health Institute (ISP Chile, number N° 20674/21).
    Consent: Written informed consent was obtained from the parent(s) or legal representative(s) of the child before enrollment.
    Sex as a biological variablenot detected.
    RandomizationStudy design: This study is a global multi-center, randomized, double-blinded, and placebo-controlled phase 3 clinical trial that aims to assess the safety, efficacy, and immunogenicity of CoronaVac® among children aged six months to 17 years.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Evaluation of specific antibody levels and their neutralization capacity: IgG anti-S1-RBD of SARS-CoV-2 were tested using ADVIA Centaur® XP SARS-CoV-2 IgG (sCOVG, Siemens)15,16, an automated two-step sandwich antibody-binding immunoassays using indirect chemiluminescence.
    anti-S1-RBD
    suggested: None
    The presence of circulating antibodies able to block the interaction of the RBD of the S1 subunit of the SARS-CoV-2 Spike protein with the recombinant human Angiotensin 2 Receptor (hACE2) was evaluated using a surrogate virus neutralization test (sVNT) (Genscript Cat#L00847-A).
    Angiotensin 2 Receptor (hACE2
    suggested: None
    Statistical analyses: Statistical differences for the immunogenicity results were assessed using the use of Wilcoxon test analyzed data to compare the levels of antibodies four weeks after the second dose against the pre-immune levels, whereas the Mann-Whitney test was used to compare the level of antibodies four weeks after the second dose between both age groups (Total IgG, sVNT, pVNT, and cVNT).
    Total IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cytopathic effect on Vero E6 cells was analyzed seven days after infection.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    All data were analyzed with GraphPad Prism 9.0.1.
    GraphPad Prism
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04992260RecruitingEfficacy, Immunogenicity and Safety of COVID-19 Vaccine , In…

    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 10.1101/2022.02.15.22270973v1 on medRxiv