Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: structure-activity relationship.
Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: structure-activity relationship.
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DOI：
10.1371/journal.pone.0030146
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Toth I
中科院分区：
文献类型：
--
作者：
Zaman M;Abdel-Aal AB;Fujita Y;Phillipps KS;Batzloff MR;Good MF;Toth I
化脓性链球菌（Streptococcus pyogenes，GAS）是引起多种疾病的革兰氏阳性细菌病原体。迄今为止，GAS疫苗的开发主要集中在M蛋白上。M蛋白在氨基（N）-末端高度可变（决定血清型），但在羧基（C）-末端保守。以前，来自M蛋白保守区的29个氨基酸的肽（命名为J14）被鉴定为潜在的疫苗候选物。当与免疫刺激剂共同施用时，J14能够引发识别许多GAS血清型的保护性抗体。然而，当单独施用时，该最小表位不显示免疫原性。为了克服这种免疫学无应答性，我们开发了一种由三种组分组成的自佐剂疫苗候选物：B细胞表位（J14）、通用辅助T细胞表位（P25）和由靶向Toll样受体2（TLR 2）的脂氨基酸（Laas）组成的脂质部分。在B10.BR（H-2k）小鼠中的免疫学评价证明，表位与脂质部分的点的连接以及Laa烷基链的长度对鼻内施用后的疫苗免疫原性具有深远影响。证明了以含有16个碳的烷基链的C-末端脂质部分为特征的疫苗，其中P25位于N-末端，并且J14连接至中心赖氨酸残基的侧链，能够诱导最佳抗体应答。这些发现与基于广谱J14的GAS疫苗的开发具有相当大的相关性，特别是为基于这种自佐剂脂肽技术的肽疫苗设计提供了合理的基础。
Streptococcus pyogenes (group A streptococcus, GAS) is a Gram-positive bacterial pathogen responsible for a wide variety of diseases. To date, GAS vaccine development has focused primarily on the M-protein. The M-protein is highly variable at the amino (N)-terminus (determining serotype) but is conserved at the carboxyl (C)-terminus. Previously a 29 amino acid peptide (named J14) from the conserved region of the M-protein was identified as a potential vaccine candidate. J14 was capable of eliciting protective antibodies that recognized many GAS serotypes when co-administered with immuno-stimulants. This minimal epitope however showed no immunogenicity when administered alone. In an attempt overcome this immunological non-responsiveness, we developed a self-adjuvanting vaccine candidate composed of three components: the B-cell epitope (J14), a universal helper T-cell epitope (P25) and a lipid moiety consisting of lipoamino acids (Laas) which target Toll-like receptor 2 (TLR2). Immunological evaluation in B10.BR (H-2k) mice demonstrated that the epitope attachment to the point of lipid moiety, and the length of the Laa alkyl chain have a profound effect on vaccine immunogenicity after intranasal administration. It was demonstrated that a vaccine featuring C-terminal lipid moiety containing alkyl chains of 16 carbons, with P25 located at the N-terminus, and J14 attached to the side chain of a central lysine residue was capable of inducing optimal antibody response. These findings have considerable relevance to the development of a broad spectrum J14-based GAS vaccine and in particular provided a rational basis for peptide vaccine design based on this self-adjuvanting lipopeptide technology.
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影响因子：
6.4
作者：
Batzloff, MR;Hayman, WA;Good, MF
通讯作者：
Good, MF
影响因子：
7.3
作者：
Abdel-Aal, Abu-Baker M.;Batzloff, Michael R.;Toth, Istvan
通讯作者：
Toth, Istvan
影响因子：
6.4
作者：
BenMohamed, L;Krishnan, R;Diamond, DJ
通讯作者：
Diamond, DJ
DOI：
10.1073/pnas.0406740101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Jackson, DC;Lau, YF;Brown, LE
通讯作者：
Brown, LE
影响因子：
5.2
作者：
Metzgar, David;McDonough, Erin A.;Russell, Kevin L.
通讯作者：
Russell, Kevin L.