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

Alessandro Gori, Claudio Peri, Giacomo Quilici, Arnone Nithichanon, Davide Gaudesi, Renato Longhi, Louise Gourlay, Martino Bolognesi, Ganjana Lertmemongkolchai, Giovanna Musco, Giorgio Colombo

Research output: Contribution to journalArticle

Abstract

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 PalBp (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.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalACS Infectious Diseases
Volume2
Issue number3
DOIs
Publication statusPublished - Mar 11 2016

Keywords

  • antigen design
  • bioprobes
  • epitope engineering
  • melioidosis
  • peptide stapling
  • structural vaccinology

ASJC Scopus subject areas

  • Infectious Diseases

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    Gori, A., Peri, C., Quilici, G., Nithichanon, A., Gaudesi, D., Longhi, R., Gourlay, L., Bolognesi, M., Lertmemongkolchai, G., Musco, G., & Colombo, G. (2016). Flexible vs Rigid Epitope Conformations for Diagnostic- and Vaccine-Oriented Applications: Novel Insights from the Burkholderia pseudomallei BPSL2765 Pal3 Epitope. ACS Infectious Diseases, 2(3), 221-230. https://doi.org/10.1021/acsinfecdis.5b00118