title: Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.
abstract: 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.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, DIDE, Imperial College, London, United Kingdom.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Clapham
authors.affiliation: Oxford University Clinical Research Unit-Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Than Ha
authors.identifier: 0000-0001-5417-2738
authors.initials: TH
authors.lastname: Quyen
authors.affiliation: Oxford University Clinical Research Unit-Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Duong Thi Hue
authors.identifier: 0000-0002-1573-5697
authors.initials: DT
authors.lastname: Kien
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, DIDE, Imperial College, London, United Kingdom.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dorigatti
authors.affiliation: Oxford University Clinical Research Unit-Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom.|Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute, Melbourne, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, DIDE, Imperial College, London, United Kingdom.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Ferguson
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D000920:Antibody-Dependent Cell Cytotoxicity; D019295:Computational Biology; D003715:Dengue / Q000276:immunology* / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D018448:Models, Immunological; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012367:RNA, Viral