Utilization of Staphylococcal Immune Evasion Protein Sbi as a Novel Vaccine Adjuvant

Yi Yang, Catherine Back, Melissa Gräwert, Ayla Wahid, Harriet Denton, Rebecca Kildani, Joshua Paulin, Kristin Wörner, Wolgang Kaiser, Dmitri i. Svergun, Asel Sartbaeva, Andrew Watts, Kevin J Marchbank, Johannes Van Den Elsen

Research output: Contribution to journalArticle

3 Citations (Scopus)
63 Downloads (Pure)

Abstract

Co-ligation of the B cell antigen receptor with complement receptor 2 on B-cells via a C3d-opsonised antigen complex significantly lowers the threshold required for B cell activation. Consequently, fusions of antigens with C3d polymers have shown great potential in vaccine design. However, these linear arrays of C3d multimers do not mimic the natural opsonisation of antigens with C3d. Here we investigate the potential of using the unique complement activating characteristics of Staphylococcal immune-evasion protein Sbi to develop a pro-vaccine approach that spontaneously coats antigens
with C3 degradation products in a natural way. We show that Sbi rapidly triggers the alternative complement pathway through recruitment of complement regulators, forming tripartite complexes that act as competitive antagonists of factor H, resulting in enhanced complement consumption. These functional results are corroborated by the structure of the complement activating Sbi-III-IV:C3d:FHR-1 complex. Finally, we demonstrate that Sbi, fused with Mycobacterium tuberculosis antigen Ag85b, causes efficient opsonisation with C3 fragments, thereby enhancing the immune response
significantly beyond that of Ag85b alone, providing proof of concept for our pro-vaccine approach.
Original languageEnglish
Article number3139
Pages (from-to)1-17
Number of pages17
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 11 Jan 2019

Keywords

  • Adjuvant
  • Complement
  • Immune evasion
  • Staphycoccus aureus
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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