Synthetic bacterial lipopeptide analogs: structural requirements for adjuvanticity

被引:14
作者
Ghielmetti, M
Reschner, A
Zwicker, M
Padovan, E
机构
[1] Univ Hosp Bern, DKF Expt Rheumatol, Dept Clin Res, CH-3010 Bern, Switzerland
[2] Univ Basel Hosp, Surg Res Lab, CH-4031 Basel, Switzerland
关键词
adjuvant; CD4; CD8; dendritic cell; Pam(3)CysSerLys(4); TNF-alpha;
D O I
10.1016/j.imbio.2005.05.015
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Modern vaccines aim at conferring immune protection, independently of the nature of the etiological agent causing the disease. These new therapeutics are based on highly purified antigenic moieties that offer potential advantages over traditional vaccines, including a high degree of safety and the capacity of eliciting highly specific immune responses. In spite of these advantages however, subunit vaccines tend to be poorly immunogenic in vivo, and require the coadministration of adjuvants that indirectly enhance cellular immunity. Thus, recombinant vaccines development is dependent on the design of new molecules, non-immunogenic per se, but endowed with immune modulatory properties. Synthetic analogs of bacterial lipoproteins were described more than a decade ago, but their capacity to act as adjuvants has been only recently dissected. These low molecular weight non-immunogenic molecules can be reproducibly synthetized, are safe, and of easy handling and administration. Furthermore, new experimental data from our laboratory reveal their powerful adjuvant effect on human HLA-I/II restricted T cell responses and identify the molecular and cellular requirements for optimal adjuvanticity. (C) 2005 Elsevier GmbH. All rights reserved.
引用
收藏
页码:211 / 215
页数:5
相关论文
共 27 条
[11]   Toll-like receptor control of the adaptive immune responses [J].
Iwasaki, A ;
Medzhitov, R .
NATURE IMMUNOLOGY, 2004, 5 (10) :987-995
[12]  
Jarrossay D, 2001, EUR J IMMUNOL, V31, P3388, DOI 10.1002/1521-4141(200111)31:11<3388::AID-IMMU3388>3.0.CO
[13]  
2-Q
[14]   Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1 [J].
Manukyan, M ;
Triantafilou, K ;
Triantafilou, M ;
Mackie, A ;
Nilsen, N ;
Espevik, T ;
Wiesmüllers, KH ;
Ulmer, AJ ;
Heine, H .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (03) :911-921
[15]   Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity [J].
Marciani, DJ .
DRUG DISCOVERY TODAY, 2003, 8 (20) :934-943
[16]   Spinning molecular immunology into successful immunotherapy [J].
Pardoll, DM .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (04) :227-238
[17]   From Pasteur to genomics: progress and challenges in infectious diseases [J].
Rappuoli, R .
NATURE MEDICINE, 2004, 10 (11) :1177-1185
[18]   The ester-bonded palmitoyl side chains of Pam3CysSerLys4 lipopeptide account for its powerful adjuvanticity to HLA class I-restricted CD8+ T lymphocytes [J].
Reschner, A ;
Moretta, A ;
Landmann, R ;
Heberer, M ;
Spagnoli, GC ;
Padovan, E .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (07) :2044-2052
[19]   FINE SPECIFICITY OF CYTOTOXIC LYMPHOCYTES-T PRIMED INVIVO EITHER WITH VIRUS OR SYNTHETIC LIPOPEPTIDE VACCINE OR PRIMED INVITRO WITH PEPTIDE [J].
SCHILD, H ;
NORDA, M ;
DERES, K ;
FALK, K ;
ROTZSCHKE, O ;
WIESMULLER, KH ;
JUNG, G ;
RAMMENSEE, HG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (06) :1665-1668
[20]   Lipopolysaccharide binding protein binds to triacylated and diacylated lipopeptides and mediates innate immune responses [J].
Schröder, NWJ ;
Heine, H ;
Alexander, C ;
Manukyan, M ;
Eckert, J ;
Hamann, L ;
Göbel, UB ;
Schumann, RR .
JOURNAL OF IMMUNOLOGY, 2004, 173 (04) :2683-2691