TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses

被引：235

作者：

Schlosser, Eva ^{[1
]}

Mueller, Marc ^{[1
]}

Fischer, Stefan ^{[2
]}

Basta, Sameh ^{[3
]}

Busch, Dirk H. ^{[4
,5
]}

Gander, Bruno ^{[2
]}

Groettrup, Marcus ^{[1
,6
]}

机构：

[1] Dept Biochem, Div Immunol, D-78457 Constance, Germany

[2] ETH, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland

[3] Queens Univ, Dept Microbiol & Immunol, Kingston, ON K7L 3N6, Canada

[4] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany

[5] GSF Inst Hlth & Environm Neuherberg, Clin Cooperat Grp Immune Monitoring GSF Natl, Munich, Germany

[6] Biotechnol Inst Thurgau, CH-8274 Tagerwilen, Switzerland

来源：

VACCINE | 2008年 / 26卷 / 13期

关键词：

biodegradable microspheres; viral infection; cytotoxic T cells;

D O I：

10.1016/j.vaccine.2008.01.030

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 phagocytose pathogens leading to maturation and cross-presentation on MHC class I. We found that the efficiency of cross-priming in mice after vaccination with biodegradable poly(D,L-lactide-co-glycolide) microspheres (MSs) was enhanced when ovalbumin was coencapsulated together with either a CpG oligonucleotide or polyl:C as compared to co-inoculation of ovalbumin-bearing MS with soluble or separately encapsulated adjuvants. A single immunization with MS containing coencaspsulated CpG and ovalbumin yielded 9% SIINFEKL/H-2K(b) tetramer positive CTLs, production of IFN-gamma, efficient cytolysis, and protection from vaccinia virus infection. Taken together, coencapsulation of adjuvant and antigen is an important paradigm for the generation of potent CTL responses. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1626 / 1637

页数：12

共 55 条

[1] Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens [J].

Ackerman, AL ;

Kyritsis, C ;

Tampé, R ;

Cresswell, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :12889-12894

[2]

Akira S, 2006, CURR TOP MICROBIOL, V311, P1

[3] Local delivery of CpG oligodeoxynucleotides induces rapid changes in the genital mucosa and inhibits replication, but not entry, of herpes simplex virus type 2 [J].

Ashkar, AA ;

Bauer, S ;

Mitchell, WJ ;

Vieira, J ;

Rosenthal, KL .

JOURNAL OF VIROLOGY, 2003, 77 (16) :8948-8956

[4] Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro [J].

Audran, R ;

Peter, K ;

Dannull, J ;

Men, Y ;

Scandella, E ;

Groettrup, M ;

Gander, B ;

Corradin, G .

VACCINE, 2003, 21 (11-12) :1250-1255

[5] Cutting edge: Rapid in vivo killing by memory CD8 T cells [J].

Barber, DL ;

Wherry, EJ ;

Ahmed, R .

JOURNAL OF IMMUNOLOGY, 2003, 171 (01) :27-31

[6] The cross-priming pathway: A portrait of an intricate immune system [J].

Basta, S. ;

Alatery, A. .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2007, 65 (04) :311-319

[7] CROSS-PRIMING FOR A SECONDARY CYTOTOXIC RESPONSE TO MINOR H-ANTIGENS WITH H-2 CONGENIC CELLS WHICH DO NOT CROSS-REACT IN CYTOTOXIC ASSAY [J].

BEVAN, MJ .

JOURNAL OF EXPERIMENTAL MEDICINE, 1976, 143 (05) :1283-1288

[8]

BINDER D, 1991, J IMMUNOL, V146, P4301

[9] Regulation of phagosome maturation by signals from Toll-like receptors [J].

Blander, JM ;

Medzhitov, R .

SCIENCE, 2004, 304 (5673) :1014-1018

[10] Toll-dependent selection of microbial antigens for presentation by dendritic cells [J].

Blander, JM ;

Medzhitov, R .

NATURE, 2006, 440 (7085) :808-812

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