Structure-activity relationship of a series of synthetic lipopeptide self-adjuvanting group A streptococcal vaccine candidates

被引：53

作者：

Abdel-Aal, Abu-Baker M. ^{[1
]}

Batzloff, Michael R. ^{[2
]}

Fujita, Yoshio ^{[1
]}

Barozzi, Nadia ^{[1
]}

Faria, Andres ^{[1
]}

Simerska, Pavia ^{[1
]}

Moyle, Peter M. ^{[1
]}

Good, Michael F. ^{[2
]}

Toth, Istvan ^{[1
]}

机构：

[1] Univ Queensland, SMMS, St Lucia, Qld 4072, Australia

[2] Queensland Inst Med Res, Herston, Qld 4029, Australia

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 01期

关键词：

D O I：

10.1021/jm701091d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The development of 16 self-adjuvanting group A streptococcal vaccine candidates, composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG antibodies were detected following subcutaneous immunization of BALB/c (H-2(d)) mice with each construct without the need for an additional adjuvant. The effect of changing the order of P25, J14, and lipid moiety attachment or incorporation of P25 and J14 into a lipid-core peptide system on antibody titers was assessed. The point of lipid moiety attachment had the greatest influence on systemic J14-specific IgG antibody titers. Overall, the best vaccines featured a C-terminal lipid moiety, conjugated through a lysine residue to P25 at the N-terminus, and J14 on the lysine side chain.

引用

页码：167 / 172

页数：6

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