title: Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels.
abstract: Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4(+) T cells broadly reactive with drifted H5. The CD4(+) response was dominated by IL-2(+) IFN-gamma(-) IL-13(-) T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4(+) T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4(+) T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, Via Fiorentina 1, Siena 53100, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Galli
authors.forename: Duccio
authors.initials: D
authors.lastname: Medini
authors.forename: Erica
authors.initials: E
authors.lastname: Borgogni
authors.forename: Luisanna
authors.initials: L
authors.lastname: Zedda
authors.forename: Monia
authors.initials: M
authors.lastname: Bardelli
authors.forename: Carmine
authors.initials: C
authors.lastname: Malzone
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.forename: Simona
authors.initials: S
authors.lastname: Tavarini
authors.forename: Chiara
authors.initials: C
authors.lastname: Sammicheli
authors.forename: Anne K
authors.initials: AK
authors.lastname: Hilbert
authors.forename: Volker
authors.initials: V
authors.lastname: Brauer
authors.forename: Angelika
authors.initials: A
authors.lastname: Banzhoff
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology; D009500:Neutralization Tests; D010641:Phenotype; D011136:Polysorbates / Q000008:administration & dosage* / Q000494:pharmacology; D013185:Squalene / Q000008:administration & dosage* / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene