A Streptococcus pneumoniae Type 2 Oligosaccharide Glycoconjugate Elicits Opsonic Antibodies and Is Protective in an Animal Model of Invasive Pneumococcal Disease
| Autor: | Sandra-Maria Wienhold, Lennart Lykke, Katrin Reppe, Martin Witzenrath, Peter H. Seeberger, Madhu Emmadi, Marilda P. Lisboa, Claney L. Pereira, Sharavathi Guddehalli Parameswarappa, Naeem Khan |
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| Rok vydání: | 2017 |
| Předmět: |
Serotype
Glycan Glycoconjugate T-Lymphocytes Oligosaccharides 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Pneumococcal Infections Catalysis Microbiology Pneumococcal Vaccines Mice Colloid and Surface Chemistry Phagocytosis Streptococcus pneumoniae medicine Animals Humans Lung Opsonin Administration Intranasal chemistry.chemical_classification B-Lymphocytes Vaccines Conjugate biology 010405 organic chemistry Chemistry Polysaccharides Bacterial Vaccination General Chemistry bacterial infections and mycoses Antibodies Bacterial Bacterial Load 0104 chemical sciences Mice Inbred C57BL Disease Models Animal Blood Immunization biology.protein Female Rabbits Antibody Glycoconjugates |
| Zdroj: | Journal of the American Chemical Society. 139:14783-14791 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Invasive pneumococcal diseases (IPDs) remain the leading cause of vaccine-preventable childhood death, even though highly effective pneumococcal conjugate vaccines (PCVs) are used in national immunization programs in many developing countries. Licensed PCVs currently cover only 13 of the over 90 serotypes of Streptococcus pneumoniae (Sp), so nonvaccine serotypes are a major obstacle to the effective control of IPD. Sp serotype 2 (ST2) is such a nonvaccine serotype that is the main cause of IPD in many countries, including Nepal, Bangladesh, and Guatemala. Glycoconjugate vaccines based on synthetic oligosaccharides instead of isolated polysaccharides offer an attractive alternative to the traditional process for PCV development. To prevent the IPDs caused by ST2, we identified an effective ST2 neoglycoconjugate vaccine candidate that was identified using a medicinal chemistry approach. Glycan microarrays containing a series of synthetic glycans resembling portions of the ST2 capsular polysaccharide (CPS) repeating unit were used to screen human and rabbit sera and identify epitope hits. Synthetic hexasaccharide 2, resembling one repeating unit (RU) of ST2 CPS, emerged as a hit from the glycan array screens. Vaccination with neoglycoconjugates consisting of hexasaccharide 2 coupled to carrier protein CRM197 stimulates a T-cell-dependent B-cell response that induced CPS-specific opsonic antibodies in mice, resulting in killing of encapsulated bacteria by phagocytic activity. Subcutaneous immunization with neoglycoconjugate protected mice from transnasal challenge with the highly virulent ST2 strain NCTC 7466 by reducing the bacterial load in lung tissue and blood. |
| Databáze: | OpenAIRE |
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