title: Superior in vitro stimulation of human CD8+ T-cells by whole virus versus split virus influenza vaccines.
abstract: Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.
authors: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Benedict R
authors: BR
authors: Halbroth
authors: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Alexander
authors: A
authors: Heil
authors: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Eva
authors: E
authors: Distler
authors: Max-Planck-Institute for Polymer Research, Mainz, Germany.
authors: Martin
authors: M
authors: Dass
authors: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Eva M
authors: EM
authors: Wagner
authors: Institute of Virology - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Bodo
authors: B
authors: Plachter
authors: Institute of Immunology - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Hans Christian
authors: HC
authors: Probst
authors: Department of Medicine I - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Dennis
authors: D
authors: Strand
authors: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors: Udo F
authors: UF
authors: Hartwig
authors: Baxter, Vienna, Austria.
authors: Anita
authors: A
authors: Karner
authors: Baxter, Vienna, Austria.
authors: Gerald
authors: G
authors: Aichinger
authors: Baxter, Vienna, Austria.
authors: Otfried
authors: O
authors: Kistner
authors: Max-Planck-Institute for Polymer Research, Mainz, Germany.
authors: Katharina
authors: K
authors: Landfester
authors: Department of Medicine III - University Medical Center of Johannes Gutenberg-University, Mainz, Germany; Department of Medicine III - University Medical Center of Regensburg, Regensburg, Germany.
authors: Wolfgang
authors: W
authors: Herr
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000145:classification / Q000235:genetics; D007252:Influenza Vaccines / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines