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

Abdel-Aal, Abu-Baker M., Zaman, Mehfuz, Fujita, Yoshio, Batzloff, Michael R., Good, Michael F. and Toth, Istvan (2010) Design of three-component vaccines against group A streptococcal infections: Importance of spatial arrangement of vaccine components. Journal of Medical Chemistry, 53 22: 8041-8046. doi:10.1021/jm1007787


Author Abdel-Aal, Abu-Baker M.
Zaman, Mehfuz
Fujita, Yoshio
Batzloff, Michael R.
Good, Michael F.
Toth, Istvan
Title Design of three-component vaccines against group A streptococcal infections: Importance of spatial arrangement of vaccine components
Journal name Journal of Medical Chemistry   Check publisher's open access policy
ISSN 0022-2623
1520-4804
Publication date 2010-11-25
Sub-type Article (original research)
DOI 10.1021/jm1007787
Volume 53
Issue 22
Start page 8041
End page 8046
Total pages 6
Place of publication NW, Washington, DC., United States
Publisher American Chemical Society
Collection year 2011
Language eng
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.© 2010 American Chemical Society.
Keyword B-cell epitopes
M-protein
T-cell
Conserved region
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sun, 19 Dec 2010, 00:09:23 EST