title: Early Transcriptome Signatures from Immunized Mouse Dendritic Cells Predict Late Vaccine-Induced T-Cell Responses.
abstract: Systems biology offers promising approaches for identifying response-specific signatures to vaccination and assessing their predictive value. Here, we designed a modelling strategy aiming to predict the quality of late T-cell responses after vaccination from early transcriptome analysis of dendritic cells. Using standardized staining with tetramer, we first quantified antigen-specific T-cell expansion 5 to 10 days after vaccination with one of a set of 41 different vaccine vectors all expressing the same antigen. Hierarchical clustering of the responses defined sets of high and low T cell response inducers. We then compared these responses with the transcriptome of splenic dendritic cells obtained 6 hours after vaccination with the same vectors and produced a random forest model capable of predicting the quality of the later antigen-specific T-cell expansion. The model also successfully predicted vector classification as low or strong T-cell response inducers of a novel set of vaccine vectors, based on the early transcriptome results obtained from spleen dendritic cells, whole spleen and even peripheral blood mononuclear cells. Finally, our model developed with mouse datasets also accurately predicted vaccine efficacy from literature-mined human datasets.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology, Immunopathology, Immunotherapy, Paris, France.|AP-HP, Clinical Investigation Center in Biotherapy, Hôpital Pitié-Salpêtrière, Paris, France.|INSERM, UMRS 959, "Immunology, Immunopathology, Immunotherapy", Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dérian
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology, Immunopathology, Immunotherapy, Paris, France.|AP-HP, Clinical Investigation Center in Biotherapy, Hôpital Pitié-Salpêtrière, Paris, France.|INSERM, UMRS 959, "Immunology, Immunopathology, Immunotherapy", Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bellier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology, Immunopathology, Immunotherapy, Paris, France.|INSERM, UMRS 959, "Immunology, Immunopathology, Immunotherapy", Paris, France.
authors.forename: Hang Phuong
authors.initials: HP
authors.lastname: Pham
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Eliza
authors.initials: E
authors.lastname: Tsitoura
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Kazazi
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology, Immunopathology, Immunotherapy, Paris, France.|INSERM, UMRS 959, "Immunology, Immunopathology, Immunotherapy", Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Huret
authors.affiliation: Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Mavromara
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology, Immunopathology, Immunotherapy, Paris, France.|AP-HP, Clinical Investigation Center in Biotherapy, Hôpital Pitié-Salpêtrière, Paris, France.|INSERM, UMRS 959, "Immunology, Immunopathology, Immunotherapy", Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology, Immunopathology, Immunotherapy, Paris, France.|AP-HP, Clinical Investigation Center in Biotherapy, Hôpital Pitié-Salpêtrière, Paris, France.|INSERM, UMRS 959, "Immunology, Immunopathology, Immunotherapy", Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Six
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007114:Immunization / Q000379:methods; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D014765:Viral Vaccines