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A Bioactive Synthetic Outer-Core Oligosaccharide Derived from a Klebsiella pneumonia Lipopolysaccharide for Bacteria

Dushen Chen1, Akhilesh K Srivastava2, Justyna Dubrochowska1

  • 1Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG, Utrecht, The Netherlands.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|January 20, 2023
PubMed

Insights

New glycoconjugate vaccines targeting carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) were synthesized. Immunization in mice produced antibodies recognizing K. pneumoniae, offering a potential new strategy against these dangerous infections.

Area of Science:

  • Microbiology
  • Immunology
  • Synthetic Chemistry

Background:

  • Carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) poses a significant threat, causing severe hospital- and community-acquired infections.
  • Existing treatment options are limited, highlighting the urgent need for novel therapeutic strategies.
  • Vaccination presents a promising avenue for controlling K. pneumoniae infections, but no approved vaccines are currently available.

Purpose of the Study:

  • To chemically synthesize outer core oligosaccharides from K. pneumoniae lipopolysaccharide (LPS).
  • To develop glycoconjugate vaccine candidates by linking synthesized oligosaccharides to carrier proteins.
  • To evaluate the immunogenicity of these vaccine candidates in a mouse model.

Main Methods:

  • Chemical synthesis of tetra- and pentasaccharides from K. pneumoniae LPS outer core.
  • Attachment of an aminopentyl linker to the synthesized oligosaccharides.
  • Conjugation of linker-equipped oligosaccharides to carrier proteins CRM197 and BSA.
  • Immunization of mice with the resulting glycoconjugate vaccine candidates.
  • Assessment of elicited antibody responses against K. pneumoniae LPS and various strains.

Main Results:

  • Successful chemical synthesis of K. pneumoniae outer core tetra- and pentasaccharides.
  • Development of glycoconjugate vaccines by conjugating oligosaccharides to CRM197 and BSA.
  • Mice immunized with these candidates generated antibodies that recognized isolated LPS and multiple K. pneumoniae strains.
  • The synthesis strategy effectively utilized orthogonal protecting groups for precise modification of monosaccharide building blocks.

Conclusions:

  • The study successfully synthesized novel K. pneumoniae outer core oligosaccharides and developed promising glycoconjugate vaccine candidates.
  • The developed vaccines elicited a robust antibody response in mice, demonstrating their potential for combating K. pneumoniae infections.
  • This work provides a foundation for developing effective vaccines against carbapenem-resistant K. pneumoniae, addressing a critical unmet medical need.
Keywords:
conjugationglycoconjugateglycosylationoligosaccharidesvaccine

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