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Published on: December 19, 2020
Glycan Microarrays Containing Synthetic Streptococcus pneumoniae CPS Fragments and Their Application to Vaccine
Paulina Kaplonek1,2, Peter H Seeberger3,4
1Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.
Insights
Developing new vaccines against Streptococcus pneumoniae, a major cause of childhood illness, is crucial. This study explores a medicinal chemistry approach using synthetic glycans for more efficient vaccine development.
Area of Science:
- Microbiology
- Immunology
- Medicinal Chemistry
Background:
- Streptococcus pneumoniae causes severe diseases like pneumonia, septicemia, and meningitis, particularly in young children.
- Over 98 serotypes of S. pneumoniae exist, differentiated by capsular polysaccharides (CPS).
- Current vaccines rely on CPS, but their isolation and processing are complex and labor-intensive.
Purpose of the Study:
- To present a medicinal chemistry strategy for developing glycoconjugate vaccines against S. pneumoniae.
- To highlight the use of synthetic glycans as an alternative to traditional CPS isolation.
- To introduce glycan arrays as a platform for identifying protective glycotopes.
Main Methods:
- Utilizing a medicinal chemistry approach for synthetic glycan antigen creation.
- Employing glycan arrays for high-throughput screening of serum samples.
- Identifying protective glycotopes for vaccine candidate development.
Main Results:
- Demonstrated the feasibility of using synthetic glycans for vaccine development.
- Showcased glycan arrays as an effective tool for identifying key antigenic determinants.
- Paved the way for a broader range of vaccine candidates targeting diverse S. pneumoniae serotypes.
Conclusions:
- Medicinal chemistry offers a promising alternative to conventional methods for pneumococcal vaccine development.
- Synthetic glycans and glycan arrays facilitate efficient identification of protective epitopes.
- This approach can accelerate the development of next-generation pneumococcal vaccines.
Abstract:
Streptococcus pneumoniae is the leading source of life-endangering diseases like pneumonia, septicemia, and meningitis, as well as a major cause of death in children under 5 years old in developing countries. At least 98 serotypes of S. pneumoniae can be distinguished based on their structurally distinct capsular polysaccharides (CPS). Currently available CPS-based pneumococcal vaccines contain serotypes most frequently associated with invasive pneumococcal diseases. The polysaccharides used in commercial conjugate-vaccines are isolated from bacteria cultures comprising many laborious and operationally challenging steps followed by depolymerization of long polysaccharides into small fragments and their conjugation to the carrier protein. The medicinal chemistry approach for glycoconjugate vaccine development offers an exciting alternative to CPS isolation for a broad range of different glycan antigens. Glycan arrays containing well-defined synthetic glycans of CPS fragments and repeating units are used as a platform for the high-throughput screening of various serum samples and identification of protective glycotopes for vaccine candidates.
