期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 38, 期 1, 页码 20-29出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200737799
关键词
CD205/DEC-205; cellular immunity; dendritic cells; LcrV; Yersinia pestis
类别
资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U54AI057158, R01AI013013, R37AI013013] Funding Source: NIH RePORTER
- NIAID NIH HHS [R01 AI013013, 5 U54 AI057158, R01 AI013013-23, U54 AI057158, AI13013] Funding Source: Medline
There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti-DEC-205/ CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC-205(+) DC in situ. We observed antigen-specific CD4(+) T cell immunity measured by intracellular staining for IFN-gamma in three different mouse strains (C57BL/6, BALB/c, and C3H/HeJ), while we could not observe such T cell responses with F1-V vaccine in alhydrogel. Using a peptide library for LcrV protein, we identified two or more distinct CD4(+) T cell mimetopes in each MHC haplotype, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly increased the efficiency for inducing IFN-gamma-producing T cells. The targeted LcrV protein induced antibody responses to a similar extent as the F1-V subunit vaccine, but Th1-dependent IgG2c and IgG2c isotypes were observed only after anti-DEC-205:LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN-gamma-producing T cells in Y.pestis infection.
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