title: Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host.
abstract: The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.
authors.affiliation: School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Ada W C
authors.initials: AW
authors.lastname: Yan
authors.affiliation: School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Pengxing
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada M3J 1P3; Modelling Infection and Immunity Lab, Centre for Disease Modelling, York Institute for Health Research, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Heffernan
authors.affiliation: Doherty Epidemiology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3010, Australia; Modelling and Simulation, Infection and Immunity Theme, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
authors.affiliation: Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Quinn
authors.affiliation: Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; School of Applied and Biomedical Sciences, Federation University, Churchill, VIC 3842, Australia; Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Laurie
authors.affiliation: School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3010, Australia; Modelling and Simulation, Infection and Immunity Theme, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia. Electronic address: jamesm@unimelb.edu.au.
authors.forename: James M
authors.initials: JM
authors.lastname: McCaw
mesh_terms: D056704:Adaptive Immunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007251:Influenza, Human / Q000276:immunology*; D018448:Models, Immunological; D019562:Viral Load / Q000276:immunology
chemical_list: D000939:Epitopes
keywords: Cytotoxic T lymphocyte; Immunology; Mathematical model; Viral dynamics