title: A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract.
abstract: Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4(+) T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α-CD205-p24 vaccine in combination with polyICLC, induced polyfunctional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α-CD205-p24 prime-boost immunization generated CD4(+) T-cell responses, heterologous prime-boost immunization with α-CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4(+) and CD8(+) T cells within the GI tract. Finally, DC-targeting enhanced the amplitude and longevity of vaccine-induced immune responses in the GI tract. This is the first report of a nasally delivered, DC-targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ruane
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.|School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Do
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Brane
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Garg
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bozzacco
authors.affiliation: Division of Obstetrics, Gynecology and Reproductive Science Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kraus
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Caskey
authors.affiliation: Oncovir, Washington, District of Columbia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Salazar
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Trumpheller
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mehandru
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D041981:Gastrointestinal Tract / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007117:Immunization, Secondary; D007369:Interferon Inducers / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015703:Antigens, CD; D000956:Antigens, Viral; C093569:DEC-205 receptor; D016655:HIV Core Protein p24; D007369:Interferon Inducers; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; C078787:NYVAC vaccine; D011956:Receptors, Cell Surface; D014765:Viral Vaccines; D054301:gag Gene Products, Human Immunodeficiency Virus; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C