Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
- Pontificia Universidad Católica de Chile, Chile
- Instituto de Salud Pública de Chile, Chile
- University of Chile, Chile
- La Jolla Institute For Allergy & Immunology, United States
- University of California, San Diego, United States
- Sinovac Biotech, China
- University College London, United Kingdom
Abstract
Background: The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile.
Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac® separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured.
Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-g and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-g secretion.
Conclusions: Immunization with CoronaVac® in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule.
Funding: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile.
Clinical trial number: NCT04651790.
Data availability
All raw data (anonymized to protect the information of volunteers) is included with the publication of this article as a supporting file. Source Data File 1 contains the numerical data used to generate all the figures.The study protocol is also available online and was previously published in doi: 10.1101/2021.03.31.21254494.
Article and author information
Author details
Funding
Ministry of Health, Government of Chile (N/A)
- Alexis M Kalergis
The Confederation of Production and Commerce, Chile (N/A)
- Alexis M Kalergis
The Millenium Institute in Immunology and Immunotherapy (ICN09_016)
- Pablo A González
- Susan M Bueno
- Alexis M Kalergis
The Innovation fund for competitiveness FIC-R 2017 (30488811-0)
- Pablo A González
- Susan M Bueno
- Alexis M Kalergis
FONDECYT Grant (1190156)
- Ricardo Soto-Rifo
FONDECYT Grant (1180798)
- Fernando Valiente-Echeverria
NIH NIAID Contract (75N93021C00016)
- Alessandro Sette
NIH NIAID Contract (75N9301900065)
- Daniela Weiskopf
- Alessandro Sette
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: This clinical trial (clinicaltrials.gov NCT04651790) is a randomized and controlled study held in Chile with eight different sites. The study protocol adhered to the current Tripartite Guidelines for Good Clinical Practices, the Declaration of Helsinki, and local regulations and was approved by the Institutional Scientific Ethical Committee of Health Sciences of the Pontificia Universidad Católica de Chile, (#200708006). The execution was approved by the Chilean Public Health Institute (#24204/20).
Reviewing Editor
- Jameel Iqbal, DaVita Labs, United States
Publication history
- Received: June 29, 2022
- Preprint posted: August 8, 2022 (view preprint)
- Accepted: October 9, 2022
- Accepted Manuscript published: October 13, 2022 (version 1)
- Version of Record published: October 25, 2022 (version 2)
Copyright
© 2022, Gálvez et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 513
- Page views
-
- 146
- Downloads
-
- 0
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
eLife 11:e81477.
https://doi.org/10.7554/eLife.81477
Further reading
-
- Cell Biology
- Immunology and Inflammation
The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.
-
- Immunology and Inflammation
Newborns are unable to reach the adult-level humoral immune response partly due to the potent immunoregulatory role of IL-10. Increased IL-10 production by neonatal B cells has been attributed to the larger population of IL-10-producting CD43+ B-1 cells in neonates. Here, we show that neonatal mouse CD43- non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal mouse CD43- non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK and Rac1. Neonatal STAT5 activation led to IL-6 production, which in turn was responsible for IL-10 production in an autocrine/paracrine fashion through the activation of STAT3. In addition to the increased IL-6 production in response to BCR stimulation, elevated expression of IL-6Rα expression in neonatal B cells rendered them highly susceptible to IL-6 mediated STAT3 phosphorylation and IL-10 production. Finally, IL-10 secreted from neonatal mouse CD43- non-B-1 cells was sufficient to inhibit TNF-α secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19+CD43- B cells.
