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Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection

Vaccines that elicit protective cytotoxic T lymphocytes (CTL) may improve on or augment those designed primarily to elicit antibody responses. However, we have little basis for estimating the numbers of CTL required for sterilising immunity at an infection site. To address this we begin with a theor...

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Autores principales: Yates, Andrew J., Van Baalen, Minus, Antia, Rustom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219614/
https://www.ncbi.nlm.nih.gov/pubmed/22125483
http://dx.doi.org/10.1371/journal.pcbi.1002274
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author Yates, Andrew J.
Van Baalen, Minus
Antia, Rustom
author_facet Yates, Andrew J.
Van Baalen, Minus
Antia, Rustom
author_sort Yates, Andrew J.
collection PubMed
description Vaccines that elicit protective cytotoxic T lymphocytes (CTL) may improve on or augment those designed primarily to elicit antibody responses. However, we have little basis for estimating the numbers of CTL required for sterilising immunity at an infection site. To address this we begin with a theoretical estimate obtained from measurements of CTL surveillance rates and the growth rate of a virus. We show how this estimate needs to be modified to account for (i) the dynamics of CTL-infected cell conjugates, and (ii) features of the virus lifecycle in infected cells. We show that provided the inoculum size of the virus is low, the dynamics of CTL-infected cell conjugates can be ignored, but knowledge of virus life-histories is required for estimating critical thresholds of CTL densities. We show that accounting for virus replication strategies increases estimates of the minimum density of CTL required for immunity over those obtained with the canonical model of virus dynamics, and demonstrate that this modeling framework allows us to predict and compare the ability of CTL to control viruses with different life history strategies. As an example we predict that lytic viruses are more difficult to control than budding viruses when net reproduction rates and infected cell lifetimes are controlled for. Further, we use data from acute SIV infection in rhesus macaques to calculate a lower bound on the density of CTL that a vaccine must generate to control infection at the entry site. We propose that critical CTL densities can be better estimated either using quantitative models incorporating virus life histories or with in vivo assays using virus-infected cells rather than peptide-pulsed targets.
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spelling pubmed-32196142011-11-28 Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection Yates, Andrew J. Van Baalen, Minus Antia, Rustom PLoS Comput Biol Research Article Vaccines that elicit protective cytotoxic T lymphocytes (CTL) may improve on or augment those designed primarily to elicit antibody responses. However, we have little basis for estimating the numbers of CTL required for sterilising immunity at an infection site. To address this we begin with a theoretical estimate obtained from measurements of CTL surveillance rates and the growth rate of a virus. We show how this estimate needs to be modified to account for (i) the dynamics of CTL-infected cell conjugates, and (ii) features of the virus lifecycle in infected cells. We show that provided the inoculum size of the virus is low, the dynamics of CTL-infected cell conjugates can be ignored, but knowledge of virus life-histories is required for estimating critical thresholds of CTL densities. We show that accounting for virus replication strategies increases estimates of the minimum density of CTL required for immunity over those obtained with the canonical model of virus dynamics, and demonstrate that this modeling framework allows us to predict and compare the ability of CTL to control viruses with different life history strategies. As an example we predict that lytic viruses are more difficult to control than budding viruses when net reproduction rates and infected cell lifetimes are controlled for. Further, we use data from acute SIV infection in rhesus macaques to calculate a lower bound on the density of CTL that a vaccine must generate to control infection at the entry site. We propose that critical CTL densities can be better estimated either using quantitative models incorporating virus life histories or with in vivo assays using virus-infected cells rather than peptide-pulsed targets. Public Library of Science 2011-11-17 /pmc/articles/PMC3219614/ /pubmed/22125483 http://dx.doi.org/10.1371/journal.pcbi.1002274 Text en Yates 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yates, Andrew J.
Van Baalen, Minus
Antia, Rustom
Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
title Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
title_full Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
title_fullStr Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
title_full_unstemmed Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
title_short Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection
title_sort virus replication strategies and the critical ctl numbers required for the control of infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219614/
https://www.ncbi.nlm.nih.gov/pubmed/22125483
http://dx.doi.org/10.1371/journal.pcbi.1002274
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