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
相关论文
共 70 条
[31]   MHC class I antigen processing pathways [J].
Maffei, A ;
Papadopoulos, K ;
Harris, PE .
HUMAN IMMUNOLOGY, 1997, 54 (02) :91-103
[32]  
Maino VC, 1998, CYTOMETRY, V34, P207, DOI 10.1002/(SICI)1097-0320(19981015)34:5<207::AID-CYTO1>3.0.CO
[33]  
2-J
[34]   Enhancement of immune response to naked DNA vaccine by immunization with transfected dendritic cells [J].
Manickan, E ;
Kanangat, S ;
Rouse, RJD ;
Yu, ZY ;
Rouse, BT .
JOURNAL OF LEUKOCYTE BIOLOGY, 1997, 61 (02) :125-132
[35]  
Mata M, 1999, J IMMUNOL, V163, P1449
[36]   Nuclear history of a pre-mRNA determines the translational activity of cytoplasmic mRNA [J].
Matsumoto, K ;
Wassarman, KM ;
Wolffe, AP .
EMBO JOURNAL, 1998, 17 (07) :2107-2121
[37]  
MEHTADAMANI A, 1994, J IMMUNOL, V153, P996
[38]  
Minev BR, 1998, IN VIVO, V12, P629
[39]   Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA [J].
Nair, SK ;
Boczkowski, D ;
Morse, M ;
Cumming, RI ;
Lyerly, HK ;
Gilboa, E .
NATURE BIOTECHNOLOGY, 1998, 16 (04) :364-369
[40]   New millenium. The need for new vaccines [J].
Pardigon, N ;
Laouini, D .
COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES, 1999, 322 (11) :913-917