Journal Article

PreJuSER-15095

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases

Hickman, D. T.FZJ* ; López-Deber, M. P.FZJ* ; Ndao, D. M.FZJ* ; Silva, A. B.FZJ* ; Nand, D.FZJ* ; Pihlgren, M.FZJ* ; Giriens, V.FZJ* ; Madani, R.FZJ* ; St.-Pierre, A.FZJ* ; Karastan, H.FZJ* ; Nagel-Steger, L.FZJ* ; Willbold, D.FZJ* ; Riesner, D.FZJ* ; Nicolau, C.FZJ* ; Baldus, M.FZJ* ; Pfeifer, A.FZJ* ; Muhs, A.FZJ*

2011
Soc. Bethesda, Md.

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Please use a persistent id in citations: doi:10.1074/jbc.M110.186338

Abstract: Synthetic peptide immunogens that mimic the conformation of a target epitope of pathological relevance offer the possibility to precisely control the immune response specificity. Here, we performed conformational analyses using a panel of peptides in order to investigate the key parameters controlling their conformation upon integration into liposomal bilayers. These revealed that the peptide lipidation pattern, the lipid anchor chain length, and the liposome surface charge all significantly alter peptide conformation. Peptide aggregation could also be modulated post-liposome assembly by the addition of distinct small molecule β-sheet breakers. Immunization of both mice and monkeys with a model liposomal vaccine containing β-sheet aggregated lipopeptide (Palm1-15) induced polyclonal IgG antibodies that specifically recognized β-sheet multimers over monomer or non-pathological native protein. The rational design of liposome-bound peptide immunogens with defined conformation opens up the possibility to generate vaccines against a range of protein misfolding diseases, such as Alzheimer disease.

Keyword(s): Alzheimer Disease: metabolism (MeSH) ; Animals (MeSH) ; Circular Dichroism (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Immunoglobulin G: chemistry (MeSH) ; Liposomes: chemistry (MeSH) ; Magnetic Resonance Spectroscopy (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Peptides: chemistry (MeSH) ; Protein Conformation (MeSH) ; Protein Folding (MeSH) ; Protein Structure, Secondary (MeSH) ; Protein Structure, Tertiary (MeSH) ; Proteostasis Deficiencies: metabolism (MeSH) ; Thiazoles: chemistry (MeSH) ; Vaccines: chemistry (MeSH) ; Immunoglobulin G ; Liposomes ; Peptides ; Thiazoles ; Vaccines ; thioflavin T ; J

Note: Solid-state NMR studies were supported by Netherlands Organization for Scientific Research Grant 700.26.121. D.R. is a member of the Board of Directors and Scientific Advisory Board of AC Immune SA.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)
2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Appears in the scientific report 2011

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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