Humoral immune response against SARS-CoV-2 after adapted COVID-19 vaccine schedules in healthy adults: The IMCOVAS randomized clinical trial.

Anti-RBD IgG Avidity COVID-19 Humoral immunity Immunogenicity Neutralizing antibodies SARS-CoV-2 Vaccination Vaccine schedule

Journal

Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899

Informations de publication

Date de publication:
16 Jul 2024
Historique:
received: 01 02 2024
revised: 14 06 2024
accepted: 04 07 2024
medline: 18 7 2024
pubmed: 18 7 2024
entrez: 17 7 2024
Statut: aheadofprint

Résumé

To overcome supply issues of COVID-19 vaccines, this partially single blind, multi-centric, vaccine trial aimed to evaluate humoral immunogenicity using lower vaccine doses, intradermal vaccination, and heterologous vaccine schedules. Also, the immunity after a booster vaccination was assessed. 566 COVID-19-naïve healthy adults were randomized to 1 of 8 treatment arms consisting of combinations of BNT162b2, mRNA-1273, and ChAdOx1-S. Anti-Receptor-Binding Domain immunoglobulin G (RBD IgG) titers, neutralizing antibody titres, and avidity of the anti-RBD IgGs was assessed up to 1 year after study start. Prolonging the interval between vaccinations from 28 to 84 days and the use of a heterologous BNT162b2 + mRNA-1273 vaccination schedule led to a non-inferior immune response, compared to the reference schedule. A low dose of mRNA-1273 was sufficient to induce non-inferior immunity. Non-inferiority could not be demonstrated for intradermal vaccination. For all adapted vaccination schedules, anti-RBD IgG titres measured after a first booster vaccination were non-inferior to their reference schedule. This study suggests that reference vaccine schedules can be adapted without jeopardizing the development of an adequate immune response. Immunity after a booster vaccination did not depend on the dose or brand of the booster vaccine, which is relevant for future booster campaigns. The trial is registered in the European Union Clinical Trials Register (number 2021-001993-52) and on clinicaltrials.gov (NCT06189040).

Sections du résumé

BACKGROUND BACKGROUND
To overcome supply issues of COVID-19 vaccines, this partially single blind, multi-centric, vaccine trial aimed to evaluate humoral immunogenicity using lower vaccine doses, intradermal vaccination, and heterologous vaccine schedules. Also, the immunity after a booster vaccination was assessed.
METHODOLOGY METHODS
566 COVID-19-naïve healthy adults were randomized to 1 of 8 treatment arms consisting of combinations of BNT162b2, mRNA-1273, and ChAdOx1-S. Anti-Receptor-Binding Domain immunoglobulin G (RBD IgG) titers, neutralizing antibody titres, and avidity of the anti-RBD IgGs was assessed up to 1 year after study start.
RESULTS RESULTS
Prolonging the interval between vaccinations from 28 to 84 days and the use of a heterologous BNT162b2 + mRNA-1273 vaccination schedule led to a non-inferior immune response, compared to the reference schedule. A low dose of mRNA-1273 was sufficient to induce non-inferior immunity. Non-inferiority could not be demonstrated for intradermal vaccination. For all adapted vaccination schedules, anti-RBD IgG titres measured after a first booster vaccination were non-inferior to their reference schedule.
CONCLUSION CONCLUSIONS
This study suggests that reference vaccine schedules can be adapted without jeopardizing the development of an adequate immune response. Immunity after a booster vaccination did not depend on the dose or brand of the booster vaccine, which is relevant for future booster campaigns. The trial is registered in the European Union Clinical Trials Register (number 2021-001993-52) and on clinicaltrials.gov (NCT06189040).

Identifiants

pubmed: 39019657
pii: S0264-410X(24)00773-4
doi: 10.1016/j.vaccine.2024.07.018
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT06189040']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pierre Van Damme reports financial support was provided by Belgian Health Care Knowledge Centre. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper].

Auteurs

Katie Steenackers (K)

Centre for Evaluation of Vaccination, University of Antwerp, Drie Eikenstraat 663, 2650 Edegem, Belgium.

Nikita Hanning (N)

Centre for Evaluation of Vaccination, University of Antwerp, Drie Eikenstraat 663, 2650 Edegem, Belgium.

Liesbeth Bruckers (L)

Data Science Institute, UHasselt, Agoralaan Gebouw D, 3590 Diepenbeek, Belgium.

Isabelle Desombere (I)

Laboratory Immune Response, Department of Infectious Diseases in Humans, Sciensano, Rue Juliette Wytsmanstraat 14, 1050 Brussels, Belgium.

Arnaud Marchant (A)

European Plotkin Institute for Vaccinology, Université libre de Bruxelles, Rte de Lennik 900, 1070 Anderlecht, Belgium.

Kevin K Ariën (KK)

Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium.

Daphnée Georges (D)

European Plotkin Institute for Vaccinology, Université libre de Bruxelles, Rte de Lennik 900, 1070 Anderlecht, Belgium; Laboratory of Enzymology and Protein Folding, Centre for Protein Engineering, InBioS, University of Liège, Bât.B6c Quartier Agora, allée du six Août 11, 4000 Liège, Belgium.

Patrick Soentjens (P)

Department of Clinical Sciences, Institute of Tropical Medicine, Kronenburgstraat 43, 2000 Antwerp, Belgium.

Valentino D'Onofrio (V)

Center for Vaccinology, Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

Maya Hites (M)

Université libre de Bruxelles, Av. Franklin Roosevelt 50, 1050 Bruxelles, Belgium; Clinic of Infectious Diseases, Hôpital Universitaire de Bruxelles, Route de Lennik 808, 1070 Bruxelles, Belgium.

Nicole Berens-Riha (N)

Department of Clinical Sciences, Institute of Tropical Medicine, Kronenburgstraat 43, 2000 Antwerp, Belgium.

Ilse De Coster (I)

Centre for Evaluation of Vaccination, University of Antwerp, Drie Eikenstraat 663, 2650 Edegem, Belgium.

Pierre Van Damme (PV)

Centre for Evaluation of Vaccination, University of Antwerp, Drie Eikenstraat 663, 2650 Edegem, Belgium. Electronic address: pierre.vandamme@uantwerpen.be.

Classifications MeSH