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Eur J Immunol. 2008 Jan;38(1):20-9.

Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cells.

Author information

1
Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York 10065-6399, USA.

Abstract

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 IgG2a 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.

PMID:
18081041
PMCID:
PMC2864640
DOI:
10.1002/eji.200737799
[Indexed for MEDLINE]
Free PMC Article

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