Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.

Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past w...

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Main Authors: Hannah E Clapham, Than Ha Quyen, Duong Thi Hue Kien, Ilaria Dorigatti, Cameron P Simmons, Neil M Ferguson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-05-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1004951
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spelling doaj-2ec565dc245d4a2f93d631853d718e372021-04-21T15:06:07ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-05-01125e100495110.1371/journal.pcbi.1004951Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.Hannah E ClaphamThan Ha QuyenDuong Thi Hue KienIlaria DorigattiCameron P SimmonsNeil M FergusonDengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.https://doi.org/10.1371/journal.pcbi.1004951
collection DOAJ
language English
format Article
sources DOAJ
author Hannah E Clapham
Than Ha Quyen
Duong Thi Hue Kien
Ilaria Dorigatti
Cameron P Simmons
Neil M Ferguson
spellingShingle Hannah E Clapham
Than Ha Quyen
Duong Thi Hue Kien
Ilaria Dorigatti
Cameron P Simmons
Neil M Ferguson
Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
PLoS Computational Biology
author_facet Hannah E Clapham
Than Ha Quyen
Duong Thi Hue Kien
Ilaria Dorigatti
Cameron P Simmons
Neil M Ferguson
author_sort Hannah E Clapham
title Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
title_short Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
title_full Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
title_fullStr Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
title_full_unstemmed Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
title_sort modelling virus and antibody dynamics during dengue virus infection suggests a role for antibody in virus clearance.
publisher Public Library of Science (PLoS)
series PLoS Computational Biology
issn 1553-734X
1553-7358
publishDate 2016-05-01
description Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.
url https://doi.org/10.1371/journal.pcbi.1004951
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