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Characteristics of Successful Vaccine-Induced Immunity to Hepatitis C Virus.
신의철
신의철 (KAIST)
POSTECH 세미나_세미나(2009)  |  2009.09.22
T-cell responses are considered an important component of a successful HCV-vaccine. However, immunological markers that differentiate successful, vaccine-induced memory T-cells from regular memory T-cells induced during natural HCV infection have not been described.
Here, we mapped minimal T-cell epitopes, generated 6 MHC/peptide tetramers and performed a detailed multi-color flow cytometry analysis of HCV-specific memory T-cells of 5 chimpanzees, which were part of a previously published adenovirus/DNA-based HCV-NS3-5 vaccine trial (Nature Medicine 12:190, 2006). HCV-specific memory T-cells were detectable not earlier than week 11 after HCV-challenge in 2 non-vaccinated chimpanzees, whereas they were detectable immediately after vaccination in 3 vaccinated chimpanzees and their numbers increased as early as week 4 after HCV-challenge. However, irrespective of the chimpanzees’ vaccination status, HCV-specific memory T-cells wereabout 44% central memory (CCR7+CD45RA-) and 47% effector memory (CCR7-CD45RA-) cells.
At the time of their peak frequency, HCV-specific memorycells were maximally activated in non-vaccinated chimpanzees with high levels of CD38 and PD-1 expression. In contrast, HCV-specific memory cells were only modestly activated in vaccinated chimpanzees, and their activation status remained controlled even during HCV challenge. Consistent with these findings in the peripheral blood, the PD-1/CD8 mRNA ratio in the liver was higher for non-vaccinated chimpanzees than for vaccinated chimpanzees. The limited activation ofvaccine-induced T-cells was unexpected as these cells showed excellent functional responses (proliferation, IFN-g production) that were superior to those of memory T-cells induced in non-vaccinated chimpanzees during the natural course of HCV infection. Thus, vaccine-induced T-cellsappeared to achieve more (better effector function) with less effort (less activation).
Taken together, a successful T-cell vaccine induces effective T-cell immunity by optimal rather than maximal activation of HCV-specific CD8 T-cells.
본 동영상의 Citation 복사
조회 7989    주소복사 트위터 공유 페이스북 공유 
특별세미나
신의철(KAIST)
POSTECH 세미나_세미나(2009) | 2009.09.22
한경환(Michigan State University/전남대)
POSTECH 세미나_세미나(2009) | 2009.09.21
Shusuke Tada(Tohoku University)
POSTECH 세미나_세미나(2009) | 2009.05.20
백승훈(Howard Hughes Medical Institute)
POSTECH 세미나_세미나(2009) | 2009.05.20
James E. Ferrell, JR(Stanford University)
POSTECH 세미나_세미나(2009) | 2009.05.14
Christophe Robaglin(Aix-Marseille Universite)
POSTECH 세미나_세미나(2009) | 2009.05.14
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