Involvement of CD8+ T cell–mediated immune responses in LcrV DNA vaccine induced protection against lethal Y. pestis challenge

Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Vaccine (Impact Factor: 3.62). 09/2011; 29(39):6802-9. DOI: 10.1016/j.vaccine.2010.12.062
Source: PubMed


Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans.

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    • "After 72 h, the supernatants of cell cultures were collected for cytokine analysis using multiplex assay (Bio-Rad). The cells stained with CD4-phycoerythrin (PE) (clone RM4-5), CD8-allophycocyanin (APC) (clone 53-6.7) and then intracelullarly stained with IFN-fluorescein isothiocyanate (FITC) (clone XMG1.2) were analyzed by Flow cytometry as mentioned in a previous report [35]. Data was collected on a Beckman Coulter FC500 and analyzed using FCS Express 4 software. "
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    • "Recently, the involvement of the CD8+ T cell-mediated immune response in protection against Y. pestis infection was demonstrated in mice immunized with the LcrV-based DNA vaccine. The unraveling of protective T-cell epitopes within the LcrV antigen is crucial for the creation of a vaccine that can elicit optimized humoral and cell-mediated immunities.67 "
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    • "This is in contrast to B cells, which were found to be dispensable for protection, as shown by the effectiveness of anti-F1 therapy in ␮MT mice (Fig. 7). Several studies have recently demonstrated the contribution of CD4+ and CD8+ T cells to protection against plague following long-term immunization with either a live or an F1/LcrV-based vaccine [24] [39] [40]. In the current study, we extend these observations and report on the requirement for T cells for effective treatment with anti-F1 antibodies against Y. pestis infection. "
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