title: Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague.
abstract: To help design needed new vaccines for pneumonic plague, we targeted the Yersinia pestis LcrV protein directly to CD8α(+) DEC-205(+) or CD8α(-) DCIR2(+) DC along with a clinically feasible adjuvant, poly IC. By studying Y. pestis in mice, we could evaluate the capacity of this targeting approach to protect against a human pathogen. The DEC-targeted LcrV induced polarized Th1 immunity, whereas DCIR2-targeted LcrV induced fewer CD4(+) T cells secreting IFN-γ, but higher IL-4, IL-5, IL-10, and IL-13 production. DCIR-2 targeting elicited higher anti-LcrV Ab titers than DEC targeting, which were comparable to a protein vaccine given in alhydrogel adjuvant, but the latter did not induce detectable T-cell immunity. When DEC- and DCIR2-targeted and F1-V+ alhydrogel-vaccinated mice were challenged 6 wk after vaccination with the virulent CO92 Y. pestis, the protection level and Ab titers induced by DCIR2 targeting were similar to those induced by F1-V protein with alhydrogel vaccination. Therefore, LcrV targeting to DC elicits combined humoral and cellular immunity, and for the first time with this approach, also induces protection in a mouse model for a human pathogen.
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center, The Rockefeller University, New York, NY 10065-6399, USA. doy@unist.ac.kr
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Do
authors.forename: Hyein
authors.initials: H
authors.lastname: Koh
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.forename: Patrick
authors.initials: P
authors.lastname: Seo
authors.forename: S
authors.initials: S
authors.lastname: Mehandru
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
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; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000276:immunology; D014774:Virulence; D015010:Yersinia pestis / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014614:Vaccines, Synthetic