title: Emergence of new pandemic GII.4 Sydney norovirus strain correlates with escape from herd immunity.
abstract: BACKGROUND
  GII.4 noroviruses are a significant source of acute gastroenteritis worldwide, causing the majority of human norovirus outbreaks. Evolution of the GII.4 major capsid protein occurs rapidly, resulting in the emergence of new strains that produce successive waves of pandemic disease. A new pandemic isolate, GII.4 2012 Sydney, largely replaced previously circulating strains in late 2012. We compare the antigenic properties of GII.4 2012 Sydney with previously circulating strains.
  
  
  METHODS
  To determine whether GII.4-2012 Sydney is antigenically different from recently circulating strains GII.4-2006 Minerva and GII.4-2009 New Orleans in previously identified blockade epitopes, we compared reactivity and blockade profiles of GII.4-2006, GII.4-2009, and GII.4-2012 virus-like particles in surrogate neutralization/blockade assays using monoclonal antibodies and human polyclonal sera.
  
  
  RESULTS
  Using monoclonal antibodies that map to known blockade epitopes in GII.4-2006 and GII.4-2009 and human outbreak polyclonal sera, we demonstrate either complete loss or significantly reduced reactivity and blockade of GII.4.2012 compared to GII.4-2006 and GII.4-2009.
  
  
  CONCLUSIONS
  GII.4-2012 Sydney is antigenically different from GII.4-2006 Minerva and GII.4-2009 New Orleans in at least 2 key blockade epitopes. Viral evolution in key potential neutralization epitopes likely allowed GII.4-2012 to escape from human herd immunity and emerge as the new predominant strain.
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Kari
authors.initials: K
authors.lastname: Debbink
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Lindesmith
authors.forename: Eric F
authors.initials: EF
authors.lastname: Donaldson
authors.forename: Veronica
authors.initials: V
authors.lastname: Costantini
authors.forename: Martina
authors.initials: M
authors.lastname: Beltramello
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Jesica
authors.initials: J
authors.lastname: Swanstrom
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Jan
authors.initials: J
authors.lastname: Vinjé
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D005075:Biological Evolution; D017250:Caliciviridae Infections / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005759:Gastroenteritis / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D014644:Genetic Variation; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D006825:Hybridomas; D032521:Immunity, Herd; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D029322:Norovirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D058873:Pandemics; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D007074:Immunoglobulin G
keywords: GII.4 Sydney; norovirus; viral evolution; virus emergence; virus-like particles
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