Structure-Activity-Based Design of a Synthetic Malaria Peptide Eliciting Sporozoite Inhibitory Antibodies in a Virosomal Formulation

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• 作者：Shinji L. Okitsu ; Ursula Kienzl ; Kerstin Moehle ; Olivier Silvie ; Elisabetta Peduzzi ; Markus S. Mueller ; Robert  ; W. Sauerwein ; Hugues Matile ; Rinaldo Zurbriggen ; Dominique Mazier ; et al.
• 关键词：CHEMBIOL ; MICROBES
• 刊名：Chemistry & Biology
• 出版年：2007
• 出版时间：29 May 2007
• 年：2007
• 卷：14
• 期：5
• 页码：577-587
• 全文大小：838 K

文摘

Summary

The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. We describe here the design of a conformationally constrained synthetic peptide, designated UK-39, which has structural and antigenic similarity to the NPNA-repeat region of native CSP. NMR studies on the antigen support the presence of helical turn-like structures within consecutive NPNA motifs in aqueous solution. Intramuscular delivery of UK-39 to mice and rabbits on the surface of reconstituted influenza virosomes elicited high titers of sporozoite crossreactive antibodies. Influenza virus proteins were crucially important for the immunostimulatory activity of the virosome-based antigen delivery system, as a liposomal formulation of UK-39 was not immunogenic. IgG antibodies elicited by UK-39 inhibited invasion of hepatocytes by P. falciparum sporozoites, but not by antigenically distinct P. yoelii sporozoites. Our approach to optimized virosome-formulated synthetic peptide vaccines should be generally applicable for other infectious and noninfectious diseases.