Broad T Cell Immunity to the LcrV Virulence Protein is Induced by Targeted Delivery to DEC-205/CD205-Positive Mouse Dendritic Cells
ROCKEFELLER UNIV NEW YORK
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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 DEC205 DC in situ. We observed antigen-specific CD4 T cell immunity measured by intracellular staining for IFN-gamma in three different mouse strains C57BL6, BALBc, and C3FHeJ, while we could not observe such T cell respinses 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 haplotyupe, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly 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-205LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN-gamma-producing T cells in Y. pestis infection.
- Medicine and Medical Research