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Published on: December 19, 2020
Chimeric oligosaccharide conjugate induces opsonic antibodies against Streptococcus pneumoniae serotypes 19A and 19F
Someswara Rao Sanapala1, Bruna M S Seco1,2, Ju Yuel Baek1
1Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces Am Mūhlenberg 1 D-14424 Potsdam Germany peter.seeberger@mpikg.mpg.de.
Insights
A new chimeric antigen (ST19AF) successfully induced protective antibodies against Streptococcus pneumoniae 19A and 19F serotypes. This synthetic approach offers a promising strategy for developing broad-spectrum pneumococcal conjugate vaccines.
Area of Science:
- Microbiology
- Immunology
- Synthetic Chemistry
Background:
- Streptococcus pneumoniae 19A (ST19A) and 19F (ST19F) remain prevalent causes of pneumococcal disease globally, even post-PCV13 vaccine introduction.
- Current vaccines often use polysaccharide mixtures, whereas synthetic glycoconjugates offer defined chemical structures.
- Developing vaccines with minimal synthetic antigens can reduce costs and carrier protein responses.
Purpose of the Study:
- To synthesize a chimeric oligosaccharide antigen (ST19AF) capable of eliciting a protective immune response against multiple pneumococcal serotypes.
- To evaluate the immunogenicity and efficacy of the chimeric ST19AF antigen compared to single-serotype antigens.
- To demonstrate the potential of chimeric antigens in creating broad-spectrum vaccines.
Main Methods:
- Synthesis of a chimeric oligosaccharide antigen (ST19AF) combining ST19A and ST19F repeating units.
- Preparation of synthetic glycan epitopes for ST19A and ST19F individually for comparative analysis.
- Creation of semisynthetic glycoconjugates using the chimeric ST19AF antigen.
- Immunization of rabbits with the glycoconjugates and assessment of antibody titers and functional activity.
Main Results:
- Semisynthetic glycoconjugates with the chimeric ST19AF antigen induced high antibody titers in rabbits.
- The generated antibodies effectively recognized native capsular polysaccharides (CPS) from both ST19A and ST19F.
- Antibodies demonstrated bactericidal activity against both S. pneumoniae 19A and 19F strains.
Conclusions:
- Chimeric oligosaccharide antigens can successfully induce immune responses against multiple bacterial serotypes.
- The ST19AF chimeric antigen is a viable strategy for developing vaccines targeting prevalent pneumococcal serotypes.
- Synthetic chimeric antigens represent an attractive approach for generating broad-spectrum protection against pneumococcal disease.
Abstract:
Streptococcus pneumoniae 19A (ST19A) and 19F (ST19F) are among the prevalent serotypes causing pneumococcal disease worldwide even after introduction of a 13-valent pneumococcal conjugate vaccine (PCV13). Synthetic glycoconjugate vaccines have defined chemical structures rather than isolated polysaccharide mixtures utilized in marketed vaccines. Ideally, a minimal number of synthetic antigens would cover as many bacterial serotypes to lower cost of goods and minimize the response to carrier proteins. To demonstrate that a chimeric oligosaccharide antigen can induce a protective immune response against multiple serotypes, we synthesized a chimeric antigen (ST19AF) that is comprised of a repeating unit of ST19A and ST19F capsular polysaccharide each. Synthetic glycan epitopes representing only ST19A, and ST19F were prepared for comparison. Semisynthetic glycoconjugates containing chimeric antigen ST19AF induced high antibody titers able to recognize native CPS from ST19A and ST19F in rabbits. The antibodies were able to kill both strains of pneumococci. Chimeric antigens are an attractive means to induce an immune response against multiple bacterial serotypes.
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