HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response

被引:142
作者
Weissman, D
Ni, HP
Scales, D
Dude, A
Capodici, J
McGibney, K
Abdool, A
Isaacs, SN
Cannon, G
Karikó, K
机构
[1] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA
[2] Univ Penn, Div Neurosurg, Philadelphia, PA 19104 USA
关键词
D O I
10.4049/jimmunol.165.8.4710
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DC) are the major APCs involved in naive T cell activation making them prime targets of vaccine research. We observed that mRNA was efficiently transfected, resulting in superior translation in DC compared with other professional APCs, A single stimulation of T cells by HIV gag-encoded mRNA-transfected DC in vitro resulted in primary CD4(+) and CD8(+) T cell immune responses at frequencies of Ag-specific cells (5-12.5%) similar to primary immune responses observed in vivo in murine models. Additionally, mRNA transfection also delivered a maturation signal to DC, Our results demonstrated that mRNA-mediated delivery of encoded Ag to DC induced potent primary T cell responses in vitro. mRNA transfection of DC, which mediated efficient delivery of antigenic peptides to MHC class I and II molecules, as web as delivering a maturation signal to DC, has the potential to be a potent and effective anti-HIV T cell-activating vaccine.
引用
收藏
页码:4710 / 4717
页数:8
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共 70 条
[1]   The coming of age of tumour immunotherapy [J].
Ada, G .
IMMUNOLOGY AND CELL BIOLOGY, 1999, 77 (02) :180-185
[2]   DNA vaccination: Transfection and activation of dendritic cells as key events for immunity [J].
Akbari, O ;
Panjwani, N ;
Garcia, S ;
Tascon, R ;
Lowrie, D ;
Stockinger, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (01) :169-177
[3]   Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo [J].
Boczkowski, D ;
Nair, SK ;
Snyder, D ;
Gilboa, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :465-472
[4]   Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine [J].
Bronte, V ;
Carroll, MW ;
Goletz, TJ ;
Wang, M ;
Overwijk, WW ;
Marincola, F ;
Rosenberg, SA ;
Moss, B ;
Restifo, NP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (07) :3183-3188
[5]   Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope [J].
Casares, S ;
Inaba, K ;
Brumeanu, TD ;
Steinman, RM ;
Bona, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (09) :1481-1486
[6]   Antigen presentation by MHC class II molecules: Invariant chain function, protein trafficking, and the molecular basis of diverse determinant capture [J].
Castellino, F ;
Zhong, GM ;
Germain, RN .
HUMAN IMMUNOLOGY, 1997, 54 (02) :159-169
[7]   RECENT ADVANCES IN THE STUDY OF DENDRITIC CELLS AND FOLLICULAR DENDRITIC CELLS [J].
CAUX, C ;
LIU, YJ ;
BANCHEREAU, J .
IMMUNOLOGY TODAY, 1995, 16 (01) :2-4
[8]   Maturation, activation, and protection of dendritic cells induced by double-stranded RNA [J].
Cella, M ;
Salio, M ;
Sakakibara, Y ;
Langen, H ;
Julkunen, I ;
Lanzavecchia, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (05) :821-829
[9]   Compact, synthetic, vaccinia virus early/late promoter for protein expression [J].
Chakrabarti, S ;
Sisler, JR ;
Moss, B .
BIOTECHNIQUES, 1997, 23 (06) :1094-1097
[10]  
Chattergoon MA, 1998, J IMMUNOL, V160, P5707