title: Live Attenuated Influenza Vaccine in Children Induces B-Cell Responses in Tonsils.
abstract: Tonsils play a key role in eliciting immune responses against respiratory pathogens. Little is known about how tonsils contribute to the local immune response after intranasal vaccination. Here, we uniquely report the mucosal humoral responses in tonsils and saliva after intranasal live attenuated influenza vaccine (LAIV) vaccination in children.
  
  
  
  Blood, saliva, and tonsils samples were collected from 39 children before and after LAIV vaccination and from 16 age-matched, nonvaccinated controls. Serum antibody responses were determined by a hemagglutination inhibition (HI) assay. The salivary immunoglobulin A (IgA) level was measured by an enzyme-linked immunosorbent assay. Antibody-secreting cell (ASC) and memory B-cell (MBC) responses were enumerated in tonsils and blood.
  
  
  
  Significant increases were observed in levels of serum antibodies and salivary IgA to influenza A(H3N2) and influenza B virus strains as early as 14 days after vaccination but not to influenza A(H1N1). Influenza virus-specific salivary IgA levels correlated with serum HI responses, making this a new possible indicator of vaccine immunogenicity in children. LAIV augmented influenza virus-specific B-cell responses in tonsils and blood. Tonsillar MBC responses correlated with systemic MBC and serological responses. Naive children showed significant increases in MBC counts after LAIV vaccination.
  
  
  
  This is the first study to demonstrate that LAIV elicits humoral B-cell responses in tonsils of young children. Furthermore, salivary IgA analysis represents an easy method for measuring immunogenicity after vaccination.
authors.affiliation: The Influenza Center.
authors.forename: Kristin Greve-Isdahl
authors.initials: KG
authors.lastname: Mohn
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science.
authors.forename: Karl Albert
authors.initials: KA
authors.lastname: Brokstad
authors.affiliation: The Influenza Center.
authors.forename: Rishi D
authors.initials: RD
authors.lastname: Pathirana
authors.affiliation: The Influenza Center.
authors.forename: Geir
authors.initials: G
authors.lastname: Bredholt
authors.affiliation: The Influenza Center.
authors.forename: Åsne
authors.initials: Å
authors.lastname: Jul-Larsen
authors.affiliation: The Influenza Center.
authors.forename: Mai Chi
authors.initials: MC
authors.lastname: Trieu
authors.affiliation: The Influenza Center.
authors.forename: Sarah Larteley
authors.initials: SL
authors.lastname: Lartey
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena VisMederi, Siena, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Montomoli
authors.affiliation: Department of Clinical Medicine, University of Bergen Department of Pediatrics.
authors.forename: Camilla
authors.initials: C
authors.lastname: Tøndel
authors.affiliation: Department of Clinical Medicine, University of Bergen Department of Otolaryngology/Head and Neck Surgery.
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Aarstad
authors.affiliation: The Influenza Center Department of Research & Development, Haukeland University Hospital, Bergen K.G. Jebsen Center for Influenza Vaccines, University of Bergen, Norway.
authors.forename: Rebecca Jane
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000914:Antibodies, Viral / Q000032:analysis*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001769:Blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D014066:Palatine Tonsil / Q000276:immunology*; D012463:Saliva / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: LAIV; antibody-secreting cell; humoral; influenza; longevity; lymphoid tissue; memory B cell; mucosa; pediatric; saliva immune response; tonsils