Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

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• 作者：Abu-Baker M. Abdel-Aal ; Michael R. Batzloff ; Yoshio Fujita ; Nadia Barozzi ; Andres Faria ; Pavla Simerska ; Peter M. Moyle ; Michael F. Good ; Istvan Toth
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：January 10, 2008
• 年：2008
• 卷：51
• 期：1
• 页码：167 - 172
• 全文大小：100K
• 年卷期：v.51,no.1(January 10, 2008)
• ISSN：1520-4804

文摘

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.