Structure-activity relationship of lipopeptide Group A streptococcus (GAS) vaccine candidates on toll-like receptor 2

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Title Structure-activity relationship of lipopeptide Group A streptococcus (GAS) vaccine candidates on toll-like receptor 2
Author Zaman, Mehfuz; Abdel-Aal, Abu-Baker M.; Phillipps, Karen S.M.; Fujita, Yoshio; Good, Michael Francis; Toth, Istvan
Journal Name Vaccine
Year Published 2010
Place of publication United Kingdom
Publisher Elsevier
Abstract Incorporation of lipoamino acids (LAAs) into peptide structures effectively imparts self-adjuvanting activity onto otherwise ineffective immunogens. Our fully synthetic lipopeptide vaccine candidates against group A streptococcus (GAS) were composed of J14 as a target GAS B-cell epitope alongside a universal helper T-cell epitope (P25) and a LAA-based lipid moiety. In the current study, we investigated the ability of our lipopeptides to activate nuclear factor-kappaB (NF-kappaB) in a toll-like receptor-2 (TLR2)-dependent manner as the possible mode of action and reported the structure-function requirements for novel TLR2 targeting lipopeptides based on LAAs. The NF-kappaB activation was dependent on the dose and the length of the alkyl chains of the incorporated lipid moieties with the hierarchy LAA 3 (16 carbons)>LAA 2 (14 carbons)>LAA 1 (12 carbons). The position of the lipid moiety (C-terminus vs. N(epsilon)-terminus of the central lysine residue) does not significantly affect NF-kappaB activation. Lipopeptides containing different copies of LAA 3 were synthesized and the di-lipidated analogue was the most effective in NFkappaB activation.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.vaccine.2009.12.046
Volume 28
Issue Number 10
Page from 2243
Page to 2248
ISSN 0264-410X
Date Accessioned 2011-03-29
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Infectious Diseases
URI http://hdl.handle.net/10072/38011
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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