title: Masking of antigenic epitopes by antibodies shapes the humoral immune response to influenza.
abstract: The immune responses to influenza, a virus that exhibits strain variation, show complex dynamics where prior immunity shapes the response to the subsequent infecting strains. Original antigenic sin (OAS) describes the observation that antibodies to the first encountered influenza strain, specifically antibodies to the epitopes on the head of influenza's main surface glycoprotein, haemagglutinin (HA), dominate following infection with new drifted strains. OAS suggests that responses to the original strain are preferentially boosted. Recent studies also show limited boosting of the antibodies to conserved epitopes on the stem of HA, which are attractive targets for a 'universal vaccine'. We develop multi-epitope models to explore how pre-existing immunity modulates the immune response to new strains following immunization. Our models suggest that the masking of antigenic epitopes by antibodies may play an important role in describing the complex dynamics of OAS and limited boosting of antibodies to the stem of HA. Analysis of recently published data confirms model predictions for how pre-existing antibodies to an epitope on HA decrease the magnitude of boosting of the antibody response to this epitope following immunization. We explore strategies for boosting of antibodies to conserved epitopes and generating broadly protective immunity to multiple strains.
authors.affiliation: Department of Biology, Emory University, Atlanta, GA 30322, USA vizarni@emory.edu.
authors.forename: Veronika I
authors.initials: VI
authors.lastname: Zarnitsyna
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA Emory Vaccine Center, Atlanta, GA 30322, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Ellebedy
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA Emory Vaccine Center, Atlanta, GA 30322, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Davis
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA Emory Vaccine Center, Atlanta, GA 30322, USA.
authors.forename: Joshy
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA Emory Vaccine Center, Atlanta, GA 30322, USA.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Department of Biology, Emory University, Atlanta, GA 30322, USA rantia@emory.edu.
authors.forename: Rustom
authors.initials: R
authors.lastname: Antia
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology*; D055641:Mathematical Concepts; D018448:Models, Immunological; D009975:Orthomyxoviridae / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus
keywords: epitope masking model; humoral immunity; influenza; strain-variation