title: Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.
abstract: BACKGROUND
  Two doses of either trivalent live attenuated or inactivated influenza vaccines (LAIV and TIV, respectively) are approved for young children (≥ 24 months old for LAIV and ≥ 6 months old for TIV) and induce protective antibody responses. However, whether combinations of LAIV and TIV are safe and equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in children for unclear reasons.
  
  
  METHODS
  Children 6-35 months old were administered, 1 month apart, 2 doses of either TIV or LAIV, or combinations of LAIV and TIV in both prime/boost sequences. Influenza-specific antibodies were measured by hemagglutination inhibition (HAI), and T cells were studied in flow cytometric and functional assays. Highly conserved M1, M2, and NP peptides predicted to be presented by common HLA class I and II were used to stimulate interferon-γ enzyme-linked immunospot responses.
  
  
  RESULTS
  All LAIV and/or TIV combinations were well tolerated and induced similar HAI responses. In contrast, only regimens containing LAIV induced influenza-specific CD4(+), CD8(+), and γδ T cells, including T cells specific for highly conserved influenza peptides.
  
  
  CONCLUSIONS
  Prime/boost combinations of LAIV and TIV in young children were safe and induced similar protective antibodies. Only LAIV induced CD4(+), CD8(+), and γδ T cells relevant for broadly protective heterosubtypic immunity.
  
  
  BACKGROUND
  NCT00231907.
authors.affiliation: Department of Internal Medicine, Saint Louis University Vaccine and Treatment Evaluation Unit, Missouri, USA. hoftdf@slu.edu
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Babusis
authors.forename: Shewangizaw
authors.initials: S
authors.lastname: Worku
authors.forename: Charles T
authors.initials: CT
authors.lastname: Spencer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lottenbach
authors.forename: Steven M
authors.initials: SM
authors.lastname: Truscott
authors.forename: Getahun
authors.initials: G
authors.lastname: Abate
authors.forename: Isaac G
authors.initials: IG
authors.lastname: Sakala
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gerber
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: Frances
authors.initials: F
authors.lastname: Newman
authors.forename: Irene
authors.initials: I
authors.lastname: Graham
authors.forename: Edwin L
authors.initials: EL
authors.lastname: Anderson
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects / Q000379:methods; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated