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Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague

Authors
 Yoonkyung Do  ;  Hyein Koh  ;  Chae Gyu Park  ;  Diana Dudziak  ;  Patrick Seo  ;  S. Mehandru  ;  Jae-Hoon Choi  ;  Cheolho Cheong  ;  Steven Park  ;  David S. Perlin  ;  Bradford S. Powell  ;  Ralph M. Steinman 
Citation
 EUROPEAN JOURNAL OF IMMUNOLOGY, Vol.40(10) : 2791-2796, 2010 
Journal Title
 EUROPEAN JOURNAL OF IMMUNOLOGY 
ISSN
 0014-2980 
Issue Date
2010
MeSH
Adjuvants, Immunologic/pharmacology ; Animals ; Antibodies, Bacterial/blood ; Antigens, Bacterial/immunology* ; Cytokines/blood ; Immunity, Cellular/immunology ; Immunity, Humoral/immunology ; Immunization/methods* ; Mice ; Mice, Inbred BALB C ; Plague/immunology ; Plague/microbiology* ; Plague/prevention & control* ; Plague Vaccine/immunology ; Pore Forming Cytotoxic Proteins/immunology* ; Specific Pathogen-Free Organisms ; Survival Analysis ; Vaccines, Synthetic/immunology ; Virulence ; Yersinia pestis/immunology* ; Yersinia pestis/pathogenicity*
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
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/eji.201040511/abstract
DOI
10.1002/eji.201040511
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103270
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