title: CD4+ T-cell immunity after pandemic influenza vaccination cross-reacts with seasonal antigens and functionally differs from active influenza infection.
abstract: Antigen-specific antibodies are well characterized after vaccination with pandemic H1N1 or seasonal influenza vaccines. However, knowledge on cellular immunity toward pandemic H1N1 after vaccination and infection and cross-reactivities toward seasonal antigens is limited. Nineteen individuals were vaccinated with the pandemic H1N1 vaccine. Among those, ten had been prevaccinated against seasonal influenza. CD4(+)  T cells specific for pandemic H1N1 and for seasonal vaccine, and antibodies were monitored using flow cytometry and ELISA/neutralization assays, respectively. In addition, seven patients with acute pandemic influenza infection were analyzed. Pandemic H1N1 vaccination induced a strong 4.63-fold (IQR 4.16) increase in antigen-specific CD4(+)  T cells that was more pronounced in individuals not prevaccinated with seasonal influenza (p = 0.01). T-cell levels toward seasonal vaccine concomitantly rose by 2.71-fold (IQR 2.26). Likewise, prevaccination with seasonal influenza induced a less pronounced increase in specific antibodies. Influenza-specific T cells in vaccinees had a Th1 phenotype mainly coexpressing IFN-γ and IL-2, whereas patients with active pandemic influenza showed a shift toward cells predominantly expressing IFN-γ. In conclusion, T cells toward seasonal influenza antigens cross-react with pandemic H1N1 antigens and affect induction of specific T cells after pandemic influenza vaccination. In addition, the cytokine patterns of specific T cells during acute H1N1 infection and after vaccination differ, and the predominantly dual-positive cytokine profile of vaccine-induced T cells suggests sufficient functionality to confer successful virus control.
authors.affiliation: Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Schmidt
authors.forename: Jan
authors.initials: J
authors.lastname: Dirks
authors.forename: Martin
authors.initials: M
authors.lastname: Enders
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Gärtner
authors.forename: Heike
authors.initials: H
authors.lastname: Uhlmann-Schiffler
authors.forename: Urban
authors.initials: U
authors.lastname: Sester
authors.forename: Martina
authors.initials: M
authors.lastname: Sester
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008875:Middle Aged; D009500:Neutralization Tests; D058873:Pandemics / Q000517:prevention & control*; D018709:Statistics, Nonparametric
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007376:Interleukin-2; D007371:Interferon-gamma