Sequential Linkage of Carbohydrate Antigens to Mimic Capsular Polysaccharides: Toward Semisynthetic Glycoconjugate Vaccine Candidates against
| Autor: | Fei-Fei Xu, Claney L. Pereira, Bruna M. S. Seco, Andrea Grafmüller, Naresh Kottari, Peter H. Seeberger |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Serotype Glycan Glycoconjugate Synthetic antigen receptor Oligosaccharides HL-60 Cells Molecular Dynamics Simulation medicine.disease_cause Serogroup 01 natural sciences Biochemistry Epitope Microbiology 03 medical and health sciences Epitopes Antigen conjugate vaccines Streptococcus pneumoniae medicine Animals Humans chemistry.chemical_classification disease Vaccines Conjugate biology 010405 organic chemistry Chemistry pathogenesis Streptococcal Vaccines Articles 500 Naturwissenschaften und Mathematik::570 Biowissenschaften Biologie::570 Biowissenschaften Biologie General Medicine 0104 chemical sciences Mice Inbred C57BL 030104 developmental biology Carbohydrate Sequence biology.protein immune-response Molecular Medicine Female Antibody Carrier Proteins Glycoconjugates |
| Zdroj: | ACS Chemical Biology |
| ISSN: | 1554-8937 |
| Popis: | Vaccines based on isolated polysaccharides successfully protect humans from bacterial pathogens such as Streptococcus pneumoniae. Because polysaccharide production and isolation can be technically challenging, glycoconjugates containing synthetic antigens are an attractive alternative. Typically, the shortest possible oligosaccharide antigen is preferable as syntheses of longer structures are more difficult and time-consuming. Combining several protective epitopes or polysaccharide repeating units as blocks by bonds other than glycosidic linkages would greatly reduce the synthetic effort if the immunological response to the polysaccharide could be retained. To explore this concept, we bridged the well-understood and immunologically potent RU of S. pneumoniae serotype 14 (ST14) with an aliphatic spacer and conjugated it to the carrier protein CRM197. Mice immunized with the spacer-bridged glycan conjugates produced high levels of specific antibodies after just one or two vaccine doses, while the tetrasaccharide repeating unit alone required three doses. The antibodies recognized specifically ST14 CPS, while no significant antibody levels were raised against the spacer or unrelated CPS. Synthetic vaccines generated antibodies with opsonic activity. Mimicking polysaccharides by coupling repeating unit antigens via an aliphatic spacer may prove useful also for the development of other glycoconjugate vaccine candidates, thereby reducing the synthetic complexity while enhancing a faster immune response. |
| Databáze: | OpenAIRE |
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