title: Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine.
abstract: Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205-targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-gamma- and interleukin 2-producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-gamma-dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Trumpfheller
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Finke
authors.forename: Carolina B
authors.initials: CB
authors.lastname: López
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Moran
authors.forename: Bruno
authors.initials: B
authors.lastname: Moltedo
authors.forename: Helena
authors.initials: H
authors.lastname: Soares
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schlesinger
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Angela
authors.initials: A
authors.lastname: Granelli-Piperno
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D007279:Injections, Subcutaneous; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C093569:DEC-205 receptor; D015683:Gene Products, gag; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins