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Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans

A compartment model for an in-host liquid nanoparticle delivered mRNA vaccine is presented. Through non-dimensionalisation, five timescales are identified that dictate the lifetime of the vaccine in-host: decay of interferon gamma, antibody priming, autocatalytic growth, antibody peak and decay, and...

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Autores principales: Moyles, Iain R., Korosec, Chapin S., Heffernan, Jane M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149047/
https://www.ncbi.nlm.nih.gov/pubmed/37121986
http://dx.doi.org/10.1007/s00285-023-01919-3
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author Moyles, Iain R.
Korosec, Chapin S.
Heffernan, Jane M.
author_facet Moyles, Iain R.
Korosec, Chapin S.
Heffernan, Jane M.
author_sort Moyles, Iain R.
collection PubMed
description A compartment model for an in-host liquid nanoparticle delivered mRNA vaccine is presented. Through non-dimensionalisation, five timescales are identified that dictate the lifetime of the vaccine in-host: decay of interferon gamma, antibody priming, autocatalytic growth, antibody peak and decay, and interleukin cessation. Through asymptotic analysis we are able to obtain semi-analytical solutions in each of the time regimes which allows us to predict maximal concentrations and better understand parameter dependence in the model. We compare our model to 22 data sets for the BNT162b2 and mRNA-1273 mRNA vaccines demonstrating good agreement. Using our analysis, we estimate the values for each of the five timescales in each data set and predict maximal concentrations of plasma B-cells, antibody, and interleukin. Through our comparison, we do not observe any discernible differences between vaccine candidates and sex. However, we do identify an age dependence, specifically that vaccine activation takes longer and that peak antibody occurs sooner in patients aged 55 and greater.
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spelling pubmed-101490472023-05-01 Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans Moyles, Iain R. Korosec, Chapin S. Heffernan, Jane M. J Math Biol Article A compartment model for an in-host liquid nanoparticle delivered mRNA vaccine is presented. Through non-dimensionalisation, five timescales are identified that dictate the lifetime of the vaccine in-host: decay of interferon gamma, antibody priming, autocatalytic growth, antibody peak and decay, and interleukin cessation. Through asymptotic analysis we are able to obtain semi-analytical solutions in each of the time regimes which allows us to predict maximal concentrations and better understand parameter dependence in the model. We compare our model to 22 data sets for the BNT162b2 and mRNA-1273 mRNA vaccines demonstrating good agreement. Using our analysis, we estimate the values for each of the five timescales in each data set and predict maximal concentrations of plasma B-cells, antibody, and interleukin. Through our comparison, we do not observe any discernible differences between vaccine candidates and sex. However, we do identify an age dependence, specifically that vaccine activation takes longer and that peak antibody occurs sooner in patients aged 55 and greater. Springer Berlin Heidelberg 2023-04-30 2023 /pmc/articles/PMC10149047/ /pubmed/37121986 http://dx.doi.org/10.1007/s00285-023-01919-3 Text en © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Moyles, Iain R.
Korosec, Chapin S.
Heffernan, Jane M.
Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
title Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
title_full Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
title_fullStr Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
title_full_unstemmed Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
title_short Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
title_sort determination of significant immunological timescales from mrna-lnp-based vaccines in humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149047/
https://www.ncbi.nlm.nih.gov/pubmed/37121986
http://dx.doi.org/10.1007/s00285-023-01919-3
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