title: Immunization with a lentiviral vector stimulates both CD4 and CD8 T cell responses to an ovalbumin transgene.
abstract: Lentiviral vectors encoding antigens are promising vaccine candidates because they transduce dendritic cells (DC) in vivo and prime CTL responses. Here we examine their stimulation of antigen-specific CD4(+) T cells, critical for protective immunity against tumors or infectious disease. We constructed lentiviral vectors (lentivectors) expressing ovalbumin, which was secreted (OVA), cytoplasmic (OVAcyt), or fused to either invariant chain (Ii-OVA) or transferrin receptor (TfR-OVA) sequences, targeting the MHC class II presentation pathway. Murine DC infected with the various lentivectors could stimulate OT-I (CD8(+), OVA TCR transgenic) T cells and all except OVAcyt could also stimulate OT-II (CD4(+), OVA TCR transgenic) T cells in vitro. Direct injection of the OVA-, Ii-OVA-, or TfR-OVA-expressing vectors into mice resulted in a CD4(+) T cell response, as shown by expansion of adoptively transferred OT-II T cells and upregulation of CD44 on these cells. The Ii-OVA vector was the most potent inducer of IFN-gamma-secreting CD4(+) and CD8(+) T cells and was the only vector to protect mice completely from challenge with OVA-expressing tumor cells. Therefore directly injected lentivectors can stimulate CD4(+) T cells; both CD4(+) and CD8(+) responses can be enhanced by targeting the antigen to the MHC class II pathway.
authors.affiliation: Infection and Immunity, University College London, Windeyer Building, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Rowe
authors.forename: Luciene
authors.initials: L
authors.lastname: Lopes
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Ranbir
authors.initials: R
authors.lastname: Bailey
authors.forename: Isabelle
authors.initials: I
authors.lastname: Barde
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Chain
authors.forename: Mary K
authors.initials: MK
authors.lastname: Collins
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019496:Cancer Vaccines / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010047:Ovalbumin