Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague
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- Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague
- Do, Yoonkyung; Koh, Hyein; Park, Chae Gyu; Dudziak, Diana; Seo, Patrick; Mehandru, S.; Choi, Jae-Hoon; Cheong, Cheolho; Park, Steven; Perlin, David S.; Powell, Bradford S.; Steinman, Ralph M.
- CD205/DEC-205; DC; DCIR2; LcrV; Yersinia pestis
- Issue Date
- WILEY-V C H VERLAG GMBH
- EUROPEAN JOURNAL OF IMMUNOLOGY, v.40, no.10, pp.2791 - 2796
- 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 6wk 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.
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