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Synthetic low-molecular
weight lipopeptide
vaccines were produced by conjugation
of tripalmitoyl-S-glyceryl-cysteinyl-serine
(P
3
CS)
with allele-specific B-, T-helper- and CTL-epitopes. P
3
CS acts as a highly
active immunoadjuvant, activating B-cells as well as macrophages. Chemically defined
minimal vaccines with molecular masses below 5000 amu allow the production of antibodies
without any additional carrier or adjuvant and make possible an
in vivo
priming of cytotoxic
T-lymphocytes and T-helper cells. Our present research focuses on measles, HIV, HCV, and tumors.
Therapeutic lipopeptide vaccines are currently being tested in clinical trial.
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Publications:
1. G. Jung, K.-H. Wiesmüller, G. Becker, H.-J. Bühring und W.G. Bessler
(1985).
Verstärkte Produktion spezifischer Antikörper durch
Präsentation der antigenen Determinanten mit kovalent verknüpften
Lipopeptid-Mitogenen,
Angew. Chem. 97, 883-885; Angew. Chem. Int. Ed.
Engl. 24, 872-873.
2. K. Deres, H.-J. Schild, K.-H. Wiesmüller, G. Jung, and H.-G. Rammensee
(1989).
In vivo Priming of Virus Specific Cytotoxic T Lymphocyte with Synthetic Lipopeptide Vaccine,
Nature 342, 561-564.
3. K.-H. Wiesmüller, G. Jung, and G. Hess (1989).
Novel Low-Molecular-Weight Synthetic Vaccine against Foot-and-Mouth-Disease Containing
a Potent B-Cell and Macrophage Activator,
Vaccine 7, 29-
33.
4. K.-H. Wiesmüller, W.G. Bessler, and G. Jung (1992).
Solid Phase Peptide Synthesis of Lipopeptide Vaccines Eliciting Epitope-specific B-, T-Helper
and T-Killer Cell Response,
Int. J. Pept. Protein Res. 40,
255-260.
5. K.-H. Wiesmüller, G. Jung, D.Gillessen, C. Loffl, W. G. Bessler, and T.
Böltz (1991).
The Antibody Response in BALB/c Mice to the
Plasmodium falciparum
Circum-sporozoite Repetitive Epitope Covalently Coupled to Lipopeptide Analogues,
Immunology 72, 109-113.
6. H. Schild, K. Deres, K.-H. Wiesmüller, G.Jung, and H.-G. Rammensee
(1991).
Efficiency of Peptides and Lipopeptides for
in vivo
Priming of Virus-specific
Cytotoxic T-Cells,
Eur. J. Immunol. 21, 2649-2654.
7. J.W.Metzger, W.Beck, and G.Jung (1992).
Ion Spray Mass Spectrometry of Lipopeptide Vaccines,
Angew. Chem.
104, 235-237; Angew. Chem. Int. Ed. Engl. 31, 226-228.
8. R. Seifert, S. Serke, D. Huhn, W. G. Bessler, S. Hauschildt, J. Metzger, K.-H.
Wiesmüller, and G. Jung (1992).
Incomplete Functional Differentiation of HL-60 Leukemic Cells by Synthetic
Lipopeptides,
Eur. J. Biochem. 203, 143-151.
9. J.W.Metzger, W.H.Sawyer, B.Wille, L.Biesert, W.G.Bessler, and G.Jung (1993).
Interaction of Immunologically Active Lipopeptides with Membranes,
Biochim. Biophys. Acta 1149, 29-39.
10. E. Borges, K.-H. Wiesmüller, G. Jung, and P. Walden (1994).
Efficacy of Synthetic Lipopeptide Vaccines in the Induction of Cytotoxic T
Lymphocytes: Comparison of the Costimulating Support Provided by Helper T
cells and Lipoamino Acid,
J. Immunol. Methods 173, 253-263.
11. B. Kleine, W. Rapp, K.-H. Wiesmüller, M. Edinger, W. Beck, J.W. Metzger,
R. Ataulakhanov, G. Jung, and W.G. Bessler (1994)
Lipopeptide-Polyoxyethylene Conjugates as Mitogens and Adjuvants,
Immunobiol. 190, 53-66.
12. G. Jung and W.G. Bessler (1995).
Lipopeptides as Adjuvants and Integrated Adjuvanticity,
in: N.D. Zeegers,
W.J.A. Boersma, and E. Claasen (eds.), Immunological Recognition of Peptides in
Medicine and Biology, pp. 159-168, CRC, Boca Raton.
12. M. Loleit, H.G. Ihlenfeldt, J. Brünjes, G. Jung, B.
Müuller, P. Hoffmann, W.G. Bessler, M. Pierres, and G. Haas (1996)
Synthetic Peptides Coupled to the Lipotripeptide P3CSS Induce
in vivo
B- and T-helper Cell Responses to HIV-1 Reverse
Transcriptase
Immunbiol. 195, 61-76.
13. S. Schlecht, H. Mossmann, K.-H. Wiesmüller, G. Jung, and W.G. Bessler (1996)
Protection Against Bacterial Infection by Urea Extracts from Salmonella
Zentralbl. Bakteriol. 284, 559-564.
14. W.G. Bessler, W. Baier, U. v.d. Esche, P. Hoffmann, L. Heinevetter, K.-H. Wiesmüller,
and G. Jung (1997)
Bacterial Lipoproteins Constitute Efficient Novel Immunogens and Adjuvants in Parenteral
and Oral Immunization,
Behring Inst. Mitt. 98, 390-399.
15. P. Hoffmann, M. Loleit, K. Mittenbühler, W. Beck, K.-H. Wiesmüller, G. Jung,
and W.G. Bessler (1997)
Induction of an Epitope-Specific Humoral Immune Response by Lipopeptide-Hapten Conjugates:
Enhancement of the Anti-Melittin Response by a Synthetic T-helper (T
h
)-Cell Epitope
FEMS Immun. Med. Microbiol. 17, 225-234.
cojinfo@uni-tuebingen.de(cojinfo@uni-tuebingen.de) - July 23, 1997