title: Induction of pulmonary mucosal immune responses with a protein vaccine targeted to the DEC-205/CD205 receptor.
abstract: It is of great interest to develop a pneumonic plague vaccine that would induce combined humoral and cellular immunity in the lung. Here we investigate a novel approach based on targeting of dendritic cells using the DEC-205/CD205 receptor (DEC) via the intranasal route as way to improve mucosal cellular immunity to the vaccine. Intranasal administration of Yersinia pestis LcrV (V) protein fused to anti-DEC antibody together with poly IC as an adjuvant induced high frequencies of IFN-γ secreting CD4(+) T cells in the airway and lung as well as pulmonary IgG and IgA antibodies. Anti-DEC:LcrV was more efficient to induce IFN-γ/TNF-α/IL-2 secreting polyfunctional CD4(+) T cells when compared to non-targeted soluble protein vaccine. In addition, the intranasal route of immunization with anti-DEC:LcrV was associated with improved survival upon pulmonary challenge with the virulent CO92 Y. pestis. Taken together, these data indicate that targeting dendritic cells via the mucosal route is a potential new avenue for the development of a mucosal vaccine against pneumonic plague.
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center, The Rockefeller University, New York, NY 10065, United States. doy@unist.ac.kr
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Do
authors.forename: Arnaud M
authors.initials: AM
authors.lastname: Didierlaurent
authors.forename: Seongho
authors.initials: S
authors.lastname: Ryu
authors.forename: Hyein
authors.initials: H
authors.lastname: Koh
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Steven
authors.initials: S
authors.lastname: Park
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
authors.forename: Bradford S
authors.initials: BS
authors.lastname: Powell
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D015010:Yersinia pestis / Q000472:pathogenicity
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015703:Antigens, CD; C093569:DEC-205 receptor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C043908:LcrV protein, Yersinia; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D007371:Interferon-gamma; D011070:Poly I-C