Design of Three-Component Vaccines against Group A Streptococcal Infections: Importance of Spatial Arrangement of Vaccine Components

被引：29
作者：
Abdel-Aal, Abu-Baker M. [1 ]
Zaman, Mehfuz [1 ]
Fujita, Yoshio [1 ]
Batzloff, Michael R. [2 ]
Good, Michael F. [2 ]
Toth, Istvan [1 ]
机构：
[1] Univ Queensland, SCMB, Brisbane, Qld 4072, Australia
[2] Queensland Inst Med Res, Herston, Qld 4029, Australia
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 22期
基金：
英国医学研究理事会;
关键词：
B-CELL EPITOPES; M-PROTEIN; T-CELL; CONSERVED REGION; ANTIBODIES; LIPOPEPTIDE; PEPTIDE; CANDIDATES; DISEASES; IMMUNIZATION;
D O I：
10.1021/jm1007787
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 alpha-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.
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收藏
页码：8041 / 8046
页数：6
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