title: Priming Vaccination With Influenza Virus H5 Hemagglutinin Antigen Significantly Increases the Duration of T cell Responses Induced by a Heterologous H5 Booster Vaccination.
abstract: Influenza A(H5N1) virus and other avian influenza virus strains represent major pandemic threats. Like all influenza A virus strains, A(H5N1) viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity.
  
  
  
  Subjects primed with clade 1 H5 antigen, with or without adjuvant, and H5-naive individuals were boosted with clade 2 H5 antigen. The impact of priming on T cells capable of both proliferation and cytokine production after antigen restimulation was assessed.
  
  
  
  Subjects previously vaccinated with clade 1 H5 antigen developed significantly enhanced clade 2 H5 cross-reactive T cell responses detectable 6 months after vaccination with clade 2 H5 antigen. Priming dose (15 µg vs 45 or 90 µg) had no effect on magnitude of heterotypic H5 T cell responses. In contrast, age at priming negatively modulated both the magnitude and duration of heterotypic H5 T cell responses. Elderly subjects developed significantly less heterotypic H5 T cell boosting, predominantly for T cells capable of cytokine production. Adjuvant had a positive albeit weaker effect than age. The magnitude of CD4(+) interferon-γ producing T cells correlated with H5 antibody responses.
  
  
  
  H5 heterotypic priming prior to onset of an A(H5N1) pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus.
authors.affiliation: Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.affiliation: Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lottenbach
authors.affiliation: Emmes Corporation, Rockville.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Goll
authors.affiliation: Emmes Corporation, Rockville.
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.affiliation: Department of Internal Medicine, University of Iowa and Iowa City VA Healthcare System.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Winokur
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Shital M
authors.initials: SM
authors.lastname: Patel
authors.affiliation: Gamble Program for Clinical Studies, Cincinnati Children's Hospital, Ohio.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Brady
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore.
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Edwards
authors.affiliation: Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
authors.affiliation: Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.affiliation: Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Blevins
authors.affiliation: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Salomon
authors.affiliation: Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D064789:Immunity, Heterologous; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C109963:hemagglutinin, avian influenza A virus
keywords: H5N1; clade; human; influenza; prime/boost; vaccine