TY  - JOUR
AU  - Hickman, D.T.
AU  - López-Deber, M.P.
AU  - Ndao, D.M.
AU  - Silva, A.B.
AU  - Nand, D.
AU  - Pihlgren, M.
AU  - Giriens, V.
AU  - Madani, R.
AU  - St.-Pierre, A.
AU  - Karastan, H.
AU  - Nagel-Steger, L.
AU  - Willbold, D.
AU  - Riesner, D.
AU  - Nicolau, C.
AU  - Baldus, M.
AU  - Pfeifer, A.
AU  - Muhs, A.
TI  - Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases
JO  - The journal of biological chemistry
VL  - 286
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - PreJuSER-15095
SP  - 13966 - 13976
PY  - 2011
N1  - 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.
AB  - 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.
KW  - Alzheimer Disease: metabolism
KW  - Animals
KW  - Circular Dichroism
KW  - Female
KW  - Humans
KW  - Immunoglobulin G: chemistry
KW  - Liposomes: chemistry
KW  - Magnetic Resonance Spectroscopy
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Peptides: chemistry
KW  - Protein Conformation
KW  - Protein Folding
KW  - Protein Structure, Secondary
KW  - Protein Structure, Tertiary
KW  - Proteostasis Deficiencies: metabolism
KW  - Thiazoles: chemistry
KW  - Vaccines: chemistry
KW  - Immunoglobulin G (NLM Chemicals)
KW  - Liposomes (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - Thiazoles (NLM Chemicals)
KW  - Vaccines (NLM Chemicals)
KW  - thioflavin T (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21343310
C2  - pmc:PMC3077597
UR  - <Go to ISI:>//WOS:000289556200019
DO  - DOI:10.1074/jbc.M110.186338
UR  - https://juser.fz-juelich.de/record/15095
ER  -