Design of three-component vaccines against group A streptococcal infections: importance of spatial arrangement of vaccine components

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Title Design of three-component vaccines against group A streptococcal infections: importance of spatial arrangement of vaccine components
Author Abdel-Aal, Abu-Baker M.; Zaman, Mehfuz; Fujita, Yoshio; Good, Michael Francis; Batzloff, Michael Raymond; Toth, Istvan
Journal Name Journal of Medicinal Chemistry
Year Published 2010
Place of publication United States
Publisher American Chemical Society
Abstract Immunological assessment of group A streptococcal (GAS) branched lipopeptides demonstrated the impact of spatial arrangement of vaccine components on both the quality and quantity of their immune responses. Each lipopeptide was composed of three components: a GAS B-cell epitope (J14), a universal CD4+ T-cell helper epitope (P25), and an immunostimulant lipid moiety that differs only in its spatial arrangement. The best systemic immune responses were demonstrated by a lipopeptide featuring the lipid moiety at the lipopeptide C-terminus. However, this candidate did not achieve protection against bacterial challenge. The best protection (100%) was shown by a lipopeptide featuring a C-terminal J14, conjugated through a lysine residue to P25 at the N-terminus, and a lipid moiety on the lysine side chain. The former candidate features α-helical conformation required to produce protective J14-specific antibodies. Our results highlight the importance of epitope orientation and lipid position in the design of three-component synthetic vaccines.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1021/jm1007787
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
Volume 53
Issue Number 22
Page from 8041
Page to 8046
ISSN 0022-2623
Date Accessioned 2011-03-21
Date Available 2014-01-08T05:28:53Z
Language en_US
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Infectious Agents
URI http://hdl.handle.net/10072/37848
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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