Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague
| Autor: | Chae Gyu Park, Bradford S. Powell, David S. Perlin, Hyein Koh, Cheolho Cheong, Ralph M. Steinman, Saurabh Mehandru, Patrick Seo, Jae-Hoon Choi, Diana Dudziak, Steven Park, Yoonkyung Do |
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| Rok vydání: | 2010 |
| Předmět: |
Pneumonic plague
Pore Forming Cytotoxic Proteins Cellular immunity Yersinia pestis Immunology Microbiology Mice Immune system Adjuvants Immunologic Immunity parasitic diseases medicine Immunology and Allergy Animals LcrV Antigens Bacterial Immunity Cellular Mice Inbred BALB C Plague Plague Vaccine Vaccines Synthetic biology Virulence biology.organism_classification medicine.disease Virology Antibodies Bacterial Survival Analysis Immunity Humoral Specific Pathogen-Free Organisms Vaccination Plague vaccine Cytokines Immunization |
| Zdroj: | European journal of immunology. 40(10) |
| ISSN: | 1521-4141 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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