Conjugation of Synthetic Trisaccharide of Staphylococcus aureus Type 8 Capsular Polysaccharide Elicits Antibodies Recognizing Intact Bacterium

Abstract

Staphylococcus aureus causes a wide range of life-threatening diseases. One of the powerful approaches for prevention and treatment is to develop an efficient vaccine as antibiotic resistance greatly increases. S. aureus type 8 capsular polysaccharide (CP8) has shown great potential in vaccine development. An understanding of the immunogenicity of CP8 trisaccharide repeating unit is valuable for epitope-focused vaccine design and cost-efficient vaccine production. We report the chemical synthesis of conjugation-ready CP8 trisaccharide 1 bearing an amine linker, which effectively served for immunological evaluation. The trisaccharide 1-CRM197 conjugate elicited a robust immunoglobulin G (IgG) immune response in mice. Both serum antibodies and prepared monoclonal antibodies recognized S. aureus strain, demonstrating that synthetic trisaccharide 1 can be an efficient antigen for vaccine development.

First molecular characterization of capsule expression and antibiotic susceptibility profile of Staphylococcus aureus isolates from bovine mastitis in Jordan

“…The results showed a strong immune response to the chemical synthesis of conjugation-ready CP8 trisaccharide 1 in mice, demonstrating that synthetic trisaccharide 1 could be an effective antigen for vaccine development. The results of Zhao et al [9] give a new horizon for researchers to continue the development of approved CP vaccines, particularly in light of the results of our current study in Jordan, where we discovered that most of the clinical isolates are capsule genotypes (91.3%) with a predominance of CP8 (88.6%). These findings provide hope for the development of a more effective vaccine for mastitis.…”

“…Vaccines based on bacterial polysaccharides protect against many dangerous pathogens and save millions of lives annually [30]. Several trials have been undertaken to develop S. aureus CP5-and CP8-based vaccines, and a recent study by Zhao et al [9] showed the great potential of S. aureus CP8 in vaccine development. The results showed a strong immune response to the chemical synthesis of conjugation-ready CP8 trisaccharide 1 in mice, demonstrating that synthetic trisaccharide 1 could be an effective antigen for vaccine development.…”

“…However, the increased spread of antibiotic resistance [6] and the development of strains of multidrug-resistant S. aureus [7] have made infection control incredibly challenging. Due to these limitations, a possible approach to preventing and controlling bovine mastitis is the development of protective vaccines against this disease [8,9].…”

“…Staphylococcus aureus isolates that do not react with antibodies to CP1, CP2, CP5, and CP8 are defined as nontypeable (NT) [12]. CP5 and CP8 are key in vaccine research and development because antibodies against CPs opsonize S. aureus, enhancing killing by neutrophil phagocytosis [9][10][11]13]. Information concerning the geographical distribution of capsular serotypes and genotypes is crucial for the rational design and use of vaccines against S. aureus mastitis in the future.…”

Recent Advances in Stereocontrolled Mannosylation: Focus on Glycans Comprising Acidic and/or Amino Sugars

“…[127][128] This glucosylation-epimerization-oxidation approach continue finding broad applications in synthesis. Among effective recent applications are the syntheses of trisaccharide derived from membrane protein integrase (MPIase), [129][130] trisaccharide repeating unit of enterobacterial common antigen (ECA), [131] various oligosaccharides derived from Staphylococcus aureus CP5 [132][133] and CP8, [134][135][136] and Streptococcus pneumonia serotype 12A and 12F. [137] Illustrated herein is a recent example from the Demchenko group that involves the synthesis of a hexasaccharide representing two repeat units of S. aureus CP8.…”