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A novel inactivated whole-cell Pseudomonas aeruginosa vaccine that acts through the cGAS-STING pathway

Cuicui Ma1, Xiao Ma2, Boguang Jiang1

  • 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.

Signal Transduction and Targeted Therapy
|October 1, 2021
PubMed

Insights

This study reveals how X-ray inactivated Pseudomonas aeruginosa (XPa) vaccines activate dendritic cells (DCs) and T cells, offering protection against P. aeruginosa infections, including in COPD models.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Pseudomonas aeruginosa infections pose a significant global health threat, necessitating novel vaccines.
  • Current understanding of X-ray inactivated whole-cell vaccines' immunological mechanisms against P. aeruginosa is limited.
  • Previous research indicated T cell boosting by X-ray inactivated P. aeruginosa vaccines.

Purpose of the Study:

  • To elucidate the immunological mechanisms underlying the efficacy of X-ray inactivated P. aeruginosa (XPa) whole-cell vaccines.
  • To investigate the interaction of XPa with dendritic cells (DCs) and its impact on immune cell activation.
  • To evaluate the protective potential of XPa against P. aeruginosa infections in various mouse models.

Main Methods:

  • Preparation of XPa vaccine from P. aeruginosa PAO1.
  • Assessment of XPa's effects on DC maturation markers (CD86, CD80, MHCII) and pathways (cGAS-STING, Toll-like receptors).
  • Evaluation of XPa-induced T cell proliferation, immunologic memory, cytokine responses, and protection in pneumonia and COPD mouse models.

Main Results:

  • XPa contains nucleic acids and 8-hydroxyguanosine.
  • XPa promotes DC maturation, apoptosis, and pyroptosis via cGAS-STING and Toll-like receptor pathways.
  • XPa stimulates CD8+ T cell proliferation, induces immunologic memory, and elicits Th1/Th2 cytokine responses.
  • XPa vaccination reduces inflammatory factors and protects mice against P. aeruginosa PAO1 and multidrug-resistant W9 infections, including in COPD models.

Conclusions:

  • XPa vaccination elicits a protective immune response against P. aeruginosa by modulating DC function and T cell activation.
  • The study uncovers a novel mechanism for X-ray inactivated whole-cell vaccines against P. aeruginosa.
  • XPa demonstrates potential as a safe and effective vaccine candidate for preventing P. aeruginosa infections, even in vulnerable populations like COPD patients.

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