Structure-Activity Relationship for the Development of a Self-Adjuvanting Mucosally Active Lipopeptide Vaccine against Streptococcus pyogenes
Structure-Activity Relationship for the Development of a Self-Adjuvanting Mucosally Active Lipopeptide Vaccine against Streptococcus pyogenes
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DOI：
10.1021/jm301074n
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发表时间：
2012-10-11
影响因子：
7.3
通讯作者：
Toth, Istvan
中科院分区：
文献类型：
--
作者：
Zaman, Mehfuz;Abdel-Aal, Abu-Baker M.;Toth, Istvan
A组链球菌（GAS）感染可导致许多疾病，其中一些可能危及生命。口-鼻粘膜是GAS感染的主要部位，粘膜活性疫苗候选物可以形成抗病和阻断传播的GAS疫苗的基础。在本研究中，将代表B细胞表位的来自GAS M蛋白（J14）的肽与通用T细胞辅助表位和Toll样受体2靶向脂质部分一起掺入以形成脂肽构建体。通过结构活性研究，我们确定了一种候选疫苗，当鼻内给药时，在没有额外佐剂的情况下诱导J14特异性粘膜和全身抗体应答。所诱发的系统性抗体能够抑制GAS的生长。此外，J14特异性粘膜抗体与呼吸道GAS激发后咽喉定植减少相对应。这些临床前实验表明，这种脂肽可以形成最佳无针粘膜GAS疫苗的基础。
Infection with group A streptococcus (GAS) can result in a number of diseases, some of which are potentially life-threatening. The oral-nasal mucosa is a primary site of GAS infection, and a mucosally active vaccine candidate could form the basis of an antidisease and transmission-blocicing GAS vaccine. In the present study, a peptide from the GAS M protein (J14) representing a B cell epitope was incorporated alongside a universal T cell helper epitope and a Toll-like receptor 2 targeting lipid moiety to form lipopeptide constructs. Through structure activity studies, we identified a vaccine candidate that induces J14-specific mucosal and systemic antibody responses when administered intranasally without additional adjuvants. The systemic antibodies elicited were capable of inhibiting the growth of GAS. In addition, J14-specific mucosal antibodies corresponded with reduced throat colonization after respiratory GAS challenge. These preclinical experiments show that this lipopeptide could form the basis of an optimal needle-free mucosal GAS vaccine.