Structure-activity relationship of a series of synthetic lipopeptide self-adjuvanting group A streptococcal vaccine candidates
Structure-activity relationship of a series of synthetic lipopeptide self-adjuvanting group A streptococcal vaccine candidates
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DOI：
10.1021/jm701091d
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发表时间：
2008-01-10
影响因子：
7.3
通讯作者：
Toth, Istvan
中科院分区：
文献类型：
--
作者：
Abdel-Aal, Abu-Baker M.;Batzloff, Michael R.;Toth, Istvan
描述了16种自佐剂A组链球菌疫苗候选物的开发，所述候选物由（i）通用辅助T细胞表位（P25）、（ii）靶GAS B细胞表位（J14）和（iii）脂质部分组成。在用每种构建体皮下免疫BALB/c（H-2（d））小鼠后检测全身性J14特异性IgG抗体，而不需要额外的佐剂。评估改变P25、J14和脂质部分连接的顺序或将P25和J14掺入脂质-核心肽系统对抗体滴度的影响。脂质部分连接点对全身J14特异性IgG抗体滴度的影响最大。总的来说，最好的疫苗具有C-末端脂质部分，通过赖氨酸残基与N-末端的P25和赖氨酸侧链上的J14缀合。
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.