Structure鈥揂ctivity Relationship for the Development of a Self-Adjuvanting Mucosally Active Lipopeptide Vaccine against Streptococcus pyogenes

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• 作者：Mehfuz Zaman ; Abu-Baker M. Abdel-Aal ; Yoshio Fujita ; Zyta M. Ziora ; Michael R. Batzloff ; Michael F. Good ; Istvan Toth
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：October 11, 2012
• 年：2012
• 卷：55
• 期：19
• 页码：8515-8523
• 全文大小：409K
• 年卷期：v.55,no.19(October 11, 2012)
• ISSN：1520-4804

文摘

Infection with group A streptococcus (GAS) can result in a number of diseases, some of which are potentially life-threatening. The oral鈥搉asal mucosa is a primary site of GAS infection, and a mucosally active vaccine candidate could form the basis of an antidisease and transmission-blocking 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.