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

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

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.

Informations de copyright

© 2022, Gálvez, Pacheco, Schultz et al.

Déclaration de conflit d'intérêts

NG, GP, BS, FM, JS, LD, LG, DR, MR, RB, YV, DM, OV, CA, GH, CI, MU, MN, ÁR, RF, JF, JM, ER, AG, MA, FV, JG, MJ, PG, AK No competing interests declared, RS has received funding from ANID - ICM, ICN 2021_045. The author has no other competing interests to declare, DW has received funding support from the NIH under contract number 75N93019C00065. The La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. The author has no other competing interests to declare, AG The La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. The author has no other competing interests to declare, AS is a consultant for Gritstone Bio, Flow Pharma, Arcturus, Immunoscape, CellCarta, Moderna, AstraZeneca, Fortress, Repertoire, Gilead, Gerson Lehrman Group, RiverVest, MedaCorp, Guggenheim, OxfordImmunotech, and Avalia. The author has received funding support from the NIH under contract 75N93021C00016 and 75N93019C00065. The La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. The author has no other competing interests to declare, GZ, WM is a SINOVAC employee and contributed to the conceptualization of the study (clinical protocol and eCRF design), DG acts as the Executive Director of the clinical trials PedCoronaVac03CL clinical study (ClinicalTrials.gov NCT04992260) and CoronaVac03CL (ClinicalTrials.govNCT04651790) (funds to the institution), and receives research support from Millennium Institute on Immunology and Immunotherapy. The author received funding from Agencia Nacional de Investigación y Desarrollo, Fondo de Fomento al Desarrollo Científico y tecnológico. The author has no other competing interests to declare, KA acts as the Scientific Director of clinical trials PedCoronaVac03CL clinical study (ClinicalTrials.gov NCT04992260) and CoronaVac03CL (ClinicalTrials.govNCT04651790) (funds to the institution), and receives research support from Millennium Institute on Immunology and Immunotherapy. The author has received funding from Agencia Nacional de Invetsigación y Desarrollo, Fondo de Fomento al Desarrollo Cientí fico y tecnológico ID20I10082. The author has no other competing interests to declare, SB acts as the General Director of clinical trials PedCoronaVac03CL clinical study (ClinicalTrials.gov NCT04992260) and CoronaVac03CL (ClinicalTrials.govNCT04651790). The author has received funding from Agencia Nacional de Investigació n y Desarrollo (ANID) - Millennium Science Initiative Program - ICN09_016 / ICN 2021_045: Millennium Institute on Immunology and Immunotherapy (ICN09_016 / ICN 2021_045; former P09/016-F) and Agencia Nacional de Investigación y Desarrollo [FONDECYT grant numbers 1190830]. The author has no other competing interests to declare