Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial-Reference-Cited by-同舟云学术

Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial

Published:2022-10-13 Issue: Volume:11 Page:
ISSN:2050-084X
Container-title:eLife
language:en
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Author:

Gálvez Nicolás MS¹²^ORCID,Pacheco Gaspar A¹²^ORCID,Schultz Bárbara M¹²^ORCID,Melo-González Felipe¹²³^ORCID,Soto Jorge A¹²³^ORCID,Duarte Luisa F¹²^ORCID,González Liliana A¹²,Rivera-Pérez Daniela¹²,Ríos Mariana¹²,Berrios Roslye V¹²,Vázquez Yaneisi¹²,Moreno-Tapia Daniela¹²,Vallejos Omar P¹²,Andrade Catalina A¹²^ORCID,Hoppe-Elsholz Guillermo¹²,Iturriaga Carolina⁴,Urzua Marcela⁴,Navarrete María S⁵,Rojas Álvaro⁶,Fasce Rodrigo⁷,Fernández Jorge⁷,Mora Judith⁷,Ramírez Eugenio⁷,Gaete-Argel Aracelly⁸,Acevedo Mónica L¹⁸,Valiente-Echeverría Fernando⁸,Soto-Rifo Ricardo⁸,Weiskopf Daniela⁹,Grifoni Alba⁹,Sette Alessandro⁹¹⁰,Zeng Gang¹¹,Meng Weining¹²,González-Aramundiz José V¹³,Johnson Marina¹⁴,Goldblatt David¹⁴,González Pablo A¹²^ORCID,Abarca Katia¹⁴^ORCID,Bueno Susan M¹²^ORCID,Kalergis Alexis M¹²¹⁵^ORCID,

Affiliation:

1. Millennium Institute on Immunology and Immunotherapy

2. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile

3. Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello

4. Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, División de Pediatría, Escuela de Medicina, Pontificia Universidad Católica de Chile

5. Centro de Investigación Clínica UC, Pontificia Universidad Católica de Chile

6. Departamento de Enfermedades Infecciosas del Adulto, División de Medicina, Escuela de Medicina, Pontificia Universidad Católica de Chile

7. Departamento de Laboratorio Biomédico, Instituto de Salud Pública de Chile

8. Laboratory of Molecular and Cellular Virology, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile

9. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology

10. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California

11. Sinovac Biotech

12. Sinovac Life Sciences Co., Ltd.

13. Departamento de Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile

14. Department of Infection, Inflammation and Immunity, Great Ormond Street Institute of Child Health, University College London

15. Departamento de Endocrinología, Facultad de Medicina, Escuela de Medicina, Pontificia Universidad Católica de Chile

Abstract

Background:The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (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 2 (0–14 schedule) or 4 weeks (0–28 schedule); 2302 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 (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-γ and the expression of activation induced markers in CD4+ T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ 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

Funder

The Ministry of Health, Government of Chile

The Confederation of Production and Commerce (CPC), Chile

The Millennium Institute on Immunology and Immunotherapy, ANID - Millennium Science Initiative Program ICN09_016

The Innovation Fund for Competitiveness FIC-R 2017

FONDECYT grant

NIH NIAID Contract

Bill & Melinda Gates Foundation

PATH

Publisher

eLife Sciences Publications, Ltd

Subject