Superior in vitro stimulation of human CD8+ T-cells by whole virus versus split virus influenza vaccines

• Published in: PloS one Vol. 9; no. 7; p. e103392
• Main Authors: Halbroth, Benedict R, Heil, Alexander, Distler, Eva, Dass, Martin, Wagner, Eva M, Plachter, Bodo, Probst, Hans Christian, Strand, Dennis, Hartwig, Udo F, Karner, Anita, Aichinger, Gerald, Kistner, Otfried, Landfester, Katharina, Herr, Wolfgang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.07.2014; Public Library of Science (PLoS)
• Subjects: Adult; Biology and Life Sciences; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell activation; Cell Differentiation; Cross-protection; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - ultrastructure; Dendritic Cells - virology; Drug delivery systems; Endosomes - metabolism; Endosomes - virology; Formulations; Human populations; Humans; Immunologic Memory; Immunological memory; In Vitro Techniques; Influenza; Influenza A virus - classification; Influenza A virus - genetics; Influenza Vaccines - immunology; Livestock; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Memory cells; Middle Aged; Morbidity; Orthomyxoviridae - immunology; Pandemics; Proteins; Stimulation; Strains (organisms); Swine; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Vaccines; Viruses; Young Adult; Austria; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0103392

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.