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
Version 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.
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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
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