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citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform

Author

Listed:
  • Joshua L. C. Wong

    (Imperial College London)

  • Julia Sanchez-Garrido

    (Imperial College London)

  • Jaie Rattle

    (Imperial College London)

  • Jonathan Bradshaw

    (Imperial College London)

  • Vishwas Mishra

    (Imperial College London)

  • Gad Frankel

    (Imperial College London)

Abstract

Existing technologies employed to generate antibodies against bacterial polysaccharides and proteins rely on the availability of purified or synthetic antigens. Here, we present a genetics-based platform that utilises Citrobacter rodentium (CR), an enteric mouse pathogen, to both produce and present complex heterologous polysaccharides and protein antigen complexes during natural infection. As proof of concept, we use lipopolysaccharides (O), capsular polysaccharides (K) and type 3 fimbrial (T3F) antigens expressed by the WHO critical priority pathogens Klebsiella pneumoniae (KP) and Escherichia coli (EC). Following one infection cycle (28 days), CR induces specific IgG antibodies against KPO1, ECO25b, KPK2 and KPT3F. We demonstrate that the antibodies are functional in downstream applications, including protection against pathogenic KP challenge, KP capsular serotyping and KP biofilm inhibition. Whilst KP and EC antigens were used as prototypical examples, this modular platform is now readily adaptable to generate antibodies against diverse polysaccharide and protein antigens, with basic science, public health and therapeutic applications.

Suggested Citation

  • Joshua L. C. Wong & Julia Sanchez-Garrido & Jaie Rattle & Jonathan Bradshaw & Vishwas Mishra & Gad Frankel, 2025. "citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63922-0
    DOI: 10.1038/s41467-025-63922-0
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    References listed on IDEAS

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    1. Minsoo Kim & Michinaga Ogawa & Yukihiro Fujita & Yuko Yoshikawa & Takeshi Nagai & Tomohiro Koyama & Shinya Nagai & Anika Lange & Reinhard Fässler & Chihiro Sasakawa, 2009. "Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment," Nature, Nature, vol. 459(7246), pages 578-582, May.
    2. Chris Schiering & Emma Wincent & Amina Metidji & Andrea Iseppon & Ying Li & Alexandre J. Potocnik & Sara Omenetti & Colin J. Henderson & C. Roland Wolf & Daniel W. Nebert & Brigitta Stockinger, 2017. "Feedback control of AHR signalling regulates intestinal immunity," Nature, Nature, vol. 542(7640), pages 242-245, February.
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