title: Boosting of Cross-Reactive and Protection-Associated T Cells in Children After Live Attenuated Influenza Vaccination.
abstract: Live attenuated influenza vaccines (LAIVs) stimulate a multifaceted immune response including cellular immunity, which may provide protection against newly emerging strains. This study shows proof of concept that LAIVs boost preexisting, cross-reactive T cells in children to genetically diverse influenza A virus (IAV) strains to which the children had not been exposed.
  
  
  
  We studied the long-term cross-reactive T-cell response in 14 trivalent LAIV-vaccinated children using the fluorescent immunospot assay (FluoroSpot) with heterologous H1N1 and H3N2 IAVs and CD8+ peptides from the internal proteins (matrix protein 1 [M1], nucleoprotein [NP], polymerase basic protein 1 [PB1]). Serum antibody responses were determined by means of hemagglutination inhibition assay. Blood samples were collected before vaccination and up to 1 year after vaccination.
  
  
  
  Preexisting cross-reactive T cells to genetically diverse IAV strains were found in the majority of the children, which were further boosted in 50% of them after receipt of LAIV. Further analyses of these T cells showed significant increases in CD8+ T cells, mainly dominated by NP-specific responses. After vaccination with LAIV, the youngest children showed the highest increase in T-cell responses.
  
  
  
  LAIV boosts durable, cross-reactive T-cell responses in children and may have a clinically protective effect at the population level. LAIV may be a first step toward the desired universal influenza vaccine.
authors.affiliation: The Influenza Centre.|Emergency Care Clinic and.
authors.forename: Kristin G I
authors.initials: KGI
authors.lastname: Mohn
authors.affiliation: The Influenza Centre.|K. G. Jebsen Centre for Influenza Vaccines, and.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, and.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Brokstad
authors.affiliation: Jenner Institute, University of Oxford, United Kingdom.
authors.forename: Saranya
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: The Influenza Centre.|K. G. Jebsen Centre for Influenza Vaccines, and.|Department of Research & Development, Haukeland University Hospital, Bergen, Norway ; and.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D056738:Cross Protection / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: Influenza; LAIV; T-cell; cellular immune response; children; cross-reactive; heterologous; protection.; vaccine