title: Human Anti-CD40 Antibody and Poly IC:LC Adjuvant Combination Induces Potent T Cell Responses in the Lung of Nonhuman Primates.
abstract: Nonlive vaccine platforms that induce potent cellular immune responses in mucosal tissue would have broad application for vaccines against infectious diseases and tumors. Induction of cellular immunity could be optimized by targeted activation of multiple innate and costimulatory signaling pathways, such as CD40 or TLRs. In this study, we evaluated immune activation and elicitation of T cell responses in nonhuman primates after immunization with peptide Ags adjuvanted with an agonistic anti-CD40Ab, with or without the TLR3 ligand poly IC:LC. We found that i.v. administration of the anti-CD40Ab induced rapid and transient innate activation characterized by IL-12 production and upregulated costimulatory and lymph node homing molecules on dendritic cells. Using fluorescently labeled Abs for in vivo tracking, we found that the anti-CD40Ab bound to all leukocytes, except T cells, and disseminated to multiple organs. CD4(+) and CD8(+) T cell responses were significantly enhanced when the anti-CD40Ab was coadministered with poly IC:LC compared with either adjuvant given alone and were almost exclusively compartmentalized to the lung. Notably, Ag-specific T cells in the bronchoalveolar lavage were sustained at ∼5-10%. These data indicate that systemic administration of anti-CD40Ab may be particularly advantageous for vaccines and/or therapies that require T cell immunity in the lung.
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Frank
authors.initials: F
authors.lastname: Liang
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
authors.forename: Gustaf
authors.initials: G
authors.lastname: Lindgren
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden;
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Sandgren
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Quinn
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Darrah
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045 ross.kedl@ucdenver.edu Karin.Lore@ki.se.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
authors.affiliation: Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and ross.kedl@ucdenver.edu Karin.Lore@ki.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000031:analogs & derivatives; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D019013:CD40 Antigens; D014612:Vaccines; D018664:Interleukin-12; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C