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Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial

Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the saf...

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Autores principales: Pannus, Pieter, Depickère, Stéphanie, Kemlin, Delphine, Houben, Sarah, Neven, Kristof Y., Heyndrickx, Leo, Michiels, Johan, Willems, Elisabeth, De Craeye, Stéphane, Francotte, Antoine, Chaumont, Félicie, Olislagers, Véronique, Waegemans, Alexandra, Verbrugghe, Mathieu, Schmickler, Marie-Noëlle, Van Gucht, Steven, Dierick, Katelijne, Marchant, Arnaud, Desombere, Isabelle, Ariën, Kevin K., Goossens, Maria E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021431/
https://www.ncbi.nlm.nih.gov/pubmed/36962838
http://dx.doi.org/10.1371/journal.pgph.0001308
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author Pannus, Pieter
Depickère, Stéphanie
Kemlin, Delphine
Houben, Sarah
Neven, Kristof Y.
Heyndrickx, Leo
Michiels, Johan
Willems, Elisabeth
De Craeye, Stéphane
Francotte, Antoine
Chaumont, Félicie
Olislagers, Véronique
Waegemans, Alexandra
Verbrugghe, Mathieu
Schmickler, Marie-Noëlle
Van Gucht, Steven
Dierick, Katelijne
Marchant, Arnaud
Desombere, Isabelle
Ariën, Kevin K.
Goossens, Maria E.
author_facet Pannus, Pieter
Depickère, Stéphanie
Kemlin, Delphine
Houben, Sarah
Neven, Kristof Y.
Heyndrickx, Leo
Michiels, Johan
Willems, Elisabeth
De Craeye, Stéphane
Francotte, Antoine
Chaumont, Félicie
Olislagers, Véronique
Waegemans, Alexandra
Verbrugghe, Mathieu
Schmickler, Marie-Noëlle
Van Gucht, Steven
Dierick, Katelijne
Marchant, Arnaud
Desombere, Isabelle
Ariën, Kevin K.
Goossens, Maria E.
author_sort Pannus, Pieter
collection PubMed
description Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. REDU-VAC is a participant-blinded, randomised, phase 4, non-inferiority study. Adults 18–55 years old, either previously infected or infection naïve, were randomly assigned to receive 20μg/20μg (fractional dose) or 30μg/30μg (full dose) of BNT162b2. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was >0.67. Primary analysis was done on the per-protocol population, including infection naïve participants only. 145 participants were enrolled and randomized, were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540–0.944). No serious adverse events occurred. While non-inferiority of the reduced dose regimen was not demonstrated, the anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04852861).
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spelling pubmed-100214312023-03-17 Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial Pannus, Pieter Depickère, Stéphanie Kemlin, Delphine Houben, Sarah Neven, Kristof Y. Heyndrickx, Leo Michiels, Johan Willems, Elisabeth De Craeye, Stéphane Francotte, Antoine Chaumont, Félicie Olislagers, Véronique Waegemans, Alexandra Verbrugghe, Mathieu Schmickler, Marie-Noëlle Van Gucht, Steven Dierick, Katelijne Marchant, Arnaud Desombere, Isabelle Ariën, Kevin K. Goossens, Maria E. PLOS Glob Public Health Research Article Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. REDU-VAC is a participant-blinded, randomised, phase 4, non-inferiority study. Adults 18–55 years old, either previously infected or infection naïve, were randomly assigned to receive 20μg/20μg (fractional dose) or 30μg/30μg (full dose) of BNT162b2. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was >0.67. Primary analysis was done on the per-protocol population, including infection naïve participants only. 145 participants were enrolled and randomized, were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540–0.944). No serious adverse events occurred. While non-inferiority of the reduced dose regimen was not demonstrated, the anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04852861). Public Library of Science 2022-12-20 /pmc/articles/PMC10021431/ /pubmed/36962838 http://dx.doi.org/10.1371/journal.pgph.0001308 Text en © 2022 Pannus et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pannus, Pieter
Depickère, Stéphanie
Kemlin, Delphine
Houben, Sarah
Neven, Kristof Y.
Heyndrickx, Leo
Michiels, Johan
Willems, Elisabeth
De Craeye, Stéphane
Francotte, Antoine
Chaumont, Félicie
Olislagers, Véronique
Waegemans, Alexandra
Verbrugghe, Mathieu
Schmickler, Marie-Noëlle
Van Gucht, Steven
Dierick, Katelijne
Marchant, Arnaud
Desombere, Isabelle
Ariën, Kevin K.
Goossens, Maria E.
Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial
title Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial
title_full Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial
title_fullStr Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial
title_full_unstemmed Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial
title_short Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial
title_sort safety and immunogenicity of a reduced dose of the bnt162b2 mrna covid-19 vaccine (redu-vac): a single blind, randomized, non-inferiority trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021431/
https://www.ncbi.nlm.nih.gov/pubmed/36962838
http://dx.doi.org/10.1371/journal.pgph.0001308
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