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Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design

Vaccination is an effective method to protect against infectious diseases. An important consideration in any vaccine formulation is the inoculum dose, i.e., amount of antigen or live attenuated pathogen that is used. Higher levels generally lead to better stimulation of the immune response but might...

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Autores principales: Handel, Andreas, Li, Yan, McKay, Brian, Pawelek, Kasia A., Zarnitsyna, Veronika, Antia, Rustom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181424/
https://www.ncbi.nlm.nih.gov/pubmed/30273336
http://dx.doi.org/10.1371/journal.pcbi.1006505
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author Handel, Andreas
Li, Yan
McKay, Brian
Pawelek, Kasia A.
Zarnitsyna, Veronika
Antia, Rustom
author_facet Handel, Andreas
Li, Yan
McKay, Brian
Pawelek, Kasia A.
Zarnitsyna, Veronika
Antia, Rustom
author_sort Handel, Andreas
collection PubMed
description Vaccination is an effective method to protect against infectious diseases. An important consideration in any vaccine formulation is the inoculum dose, i.e., amount of antigen or live attenuated pathogen that is used. Higher levels generally lead to better stimulation of the immune response but might cause more severe side effects and allow for less population coverage in the presence of vaccine shortages. Determining the optimal amount of inoculum dose is an important component of rational vaccine design. A combination of mathematical models with experimental data can help determine the impact of the inoculum dose. We illustrate the concept of using data and models to inform inoculum dose determination for vaccines, wby fitting a mathematical model to data from influenza A virus (IAV) infection of mice and human parainfluenza virus (HPIV) infection of cotton rats at different inoculum doses. We use the model to map inoculum dose to the level of immune protection and morbidity and to explore how such a framework might be used to determine an optimal inoculum dose. We show how a framework that combines mathematical models with experimental data can be used to study the impact of inoculum dose on important outcomes such as immune protection and morbidity. Our findings illustrate that the impact of inoculum dose on immune protection and morbidity can depend on the specific pathogen and that both protection and morbidity do not necessarily increase monotonically with increasing inoculum dose. Once vaccine design goals are specified with required levels of protection and acceptable levels of morbidity, our proposed framework can help in the rational design of vaccines and determination of the optimal amount of inoculum.
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spelling pubmed-61814242018-10-25 Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design Handel, Andreas Li, Yan McKay, Brian Pawelek, Kasia A. Zarnitsyna, Veronika Antia, Rustom PLoS Comput Biol Research Article Vaccination is an effective method to protect against infectious diseases. An important consideration in any vaccine formulation is the inoculum dose, i.e., amount of antigen or live attenuated pathogen that is used. Higher levels generally lead to better stimulation of the immune response but might cause more severe side effects and allow for less population coverage in the presence of vaccine shortages. Determining the optimal amount of inoculum dose is an important component of rational vaccine design. A combination of mathematical models with experimental data can help determine the impact of the inoculum dose. We illustrate the concept of using data and models to inform inoculum dose determination for vaccines, wby fitting a mathematical model to data from influenza A virus (IAV) infection of mice and human parainfluenza virus (HPIV) infection of cotton rats at different inoculum doses. We use the model to map inoculum dose to the level of immune protection and morbidity and to explore how such a framework might be used to determine an optimal inoculum dose. We show how a framework that combines mathematical models with experimental data can be used to study the impact of inoculum dose on important outcomes such as immune protection and morbidity. Our findings illustrate that the impact of inoculum dose on immune protection and morbidity can depend on the specific pathogen and that both protection and morbidity do not necessarily increase monotonically with increasing inoculum dose. Once vaccine design goals are specified with required levels of protection and acceptable levels of morbidity, our proposed framework can help in the rational design of vaccines and determination of the optimal amount of inoculum. Public Library of Science 2018-10-01 /pmc/articles/PMC6181424/ /pubmed/30273336 http://dx.doi.org/10.1371/journal.pcbi.1006505 Text en © 2018 Handel et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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
Handel, Andreas
Li, Yan
McKay, Brian
Pawelek, Kasia A.
Zarnitsyna, Veronika
Antia, Rustom
Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
title Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
title_full Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
title_fullStr Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
title_full_unstemmed Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
title_short Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
title_sort exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181424/
https://www.ncbi.nlm.nih.gov/pubmed/30273336
http://dx.doi.org/10.1371/journal.pcbi.1006505
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