Safety and Immunogenicity of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Subgroup of Healthy Adults in Chile

  1. Susan M Bueno
  2. Katia Abarca
  3. Pablo A González
  4. Nicolás M S Gálvez
  5. Jorge A Soto
  6. Luisa F Duarte
  7. Bárbara M Schultz
  8. Gaspar A Pacheco
  9. Liliana A González
  10. Yaneisi Vázquez
  11. Mariana Ríos
  12. Felipe Melo-González
  13. Daniela Rivera-Pérez
  14. Carolina Iturriaga
  15. Marcela Urzúa
  16. Angélica Domínguez
  17. Catalina A Andrade
  18. Roslye V Berríos-Rojas
  19. Gisela Canedo-Marroquín
  20. Camila Covián
  21. Daniela Moreno-Tapia
  22. Farides Saavedra
  23. Omar P Vallejos
  24. Paulina Donato
  25. Pilar Espinoza
  26. Daniela Fuentes
  27. Marcela González
  28. Paula Guzmán
  29. Paula Muñoz Venturelli
  30. Carlos M Pérez
  31. Marcela Potin
  32. Álvaro Rojas
  33. Rodrigo A Fasce
  34. Jorge Fernández
  35. Judith Mora
  36. Eugenio Ramírez
  37. Aracelly Gaete-Argel
  38. Aarón Oyarzún-Arrau
  39. Fernando Valiente-Echeverría
  40. Ricardo Soto-Rifo
  41. Daniela Weiskopf
  42. Alessandro Sette
  43. Gang Zeng
  44. Weining Meng
  45. José V González-Aramundiz
  46. Alexis M Kalergis

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Abstract

Background

The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial.

Methods

Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18–59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity.

Results

The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18–59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2.

Conclusions

Immunization with CoronaVac in a 0–14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.

Article activity feed

  1. Version published to 10.1093/cid/ciab823
  2. ScreenIT

    SciScore for 10.1101/2021.03.31.21254494: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The trial protocol was reviewed and approved by the Institutional Scientific Ethical Committee of Health Sciences, Pontificia Universidad Católica de Chile, Approval #200708006 (Committee members: Claudia Uribe PUC/Committee president; Colomba Cofré/Committee Vice-president; Andréa Villagrán/Executive secretary; Jorge Muñoz/External Lawyer; Gustavo Kaltwasser/External member; Alysa Garay/Community representative; Marisa Torres/Public Health Department; Carolina Méndez/Speech therapy representative; Luis Villarroel/Public Health Department; Pablo Brockman/Respiratory Diseases in Children Department.
    Consent: Written informed consent was obtained from each participant before enrollment.
    RandomizationParticipants were randomly assigned to immunization with CoronaVac or injection with placebo in a 1:1 ratio.
    BlindingAll participants, blind investigators, and laboratory staff were masked to arm allocation.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    To assess the presence of anti-SARS-CoV-2 antibodies, blood samples from 39 participants obtained at days 0 (baseline), 14, 28, and 42 p.i.
    anti-SARS-CoV-2
    suggested: None
    The quantitative measurement of human IgG antibodies against the RBD domain of the S1 protein (S1-RBD) and against the N protein of SARS-CoV-2 was determined using the RayBio COVID-19 (SARS-CoV-2) Human Antibody Detection Kit (Indirect ELISA method) (Cat #IEQ-CoVS1RBD-IgG & #IEQ-CovN-IgG).
    human IgG
    suggested: (Virostat Cat# 3862, RRID:AB_2889989)
    #IEQ-CovN-IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Unsolicited AEs with a frequency of 1% or more; SAEs; and Events of Special Interest are presented.
    SAEs
    suggested: (PharmaSages, RRID:SCR_012322)
    All data were analyzed with GraphPad Prism 9.0.1. or SPSS 17.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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
    NCT04651790RecruitingEfficacy, Safety, and Immunogenicity of Two Vaccination Sche…

    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.

    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 10.1101/2021.03.31.21254494 on medRxiv