Flexible vs Rigid Epitope Conformations for Diagnostic- and Vaccine-Oriented Applications: Novel Insights from the Burkholderia pseudomallei BPSL2765 Pal3 Epitope

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• 作者：Alessandro Gori ; Claudio Peri ; Giacomo Quilici ; Arnone Nithichanon ; Davide Gaudesi ; Renato Longhi ; Louise Gourlay ; Martino Bolognesi ; Ganjana Lertmemongkolchai ; Giovanna Musco ; Giorgio Colombo
• 刊名：ACS Infectious Diseases
• 出版年：2016
• 出版时间：March 11, 2016
• 年：2016
• 卷：2
• 期：3
• 页码：221-230
• 全文大小：487K
• ISSN：2373-8227

文摘

Peptides seldom retain stable conformations if separated from their native protein structure. In an immunological context, this potentially affects the development of selective peptide-based bioprobes and, from a vaccine perspective, poses inherent limits in the elicitation of cross-reactive antibodies by candidate epitopes. Here, a 1,4-disubstituted-1,2,3-triazole-mediated stapling strategy was used to stabilize the native α-helical fold of the Pal3 peptidic epitope from the protein antigen Pal_Bp (BPSL2765) from Burkholderia pseudomallei, the etiological agent of melioidosis. Whereas Pal3 shows no propensity to fold outside its native protein context, the engineered peptide (Pal3H) forms a stable α-helix, as assessed by MD, NMR, and CD structural analyses. Importantly, Pal3H shows an enhanced ability to discriminate between melioidosis patient subclasses in immune sera reactivity tests, demonstrating the potential of the stapled peptide for diagnostic purposes. With regard to antibody elicitation and related bactericidal activities, the linear peptide is shown to elicit a higher response. On these bases, we critically discuss the implications of epitope structure engineering for diagnostic- and vaccine-oriented applications.