A semisynthetic carbohydrate-lipid vaccine that protects against S. pneumoniae in mice
| Autor: | Regine Landmann, Alexander Adibekian, Thomas M A Gronewold, Artem Kalinichenko, Lucia Mori, Dominea C. K. Rathwell, Gennaro De Libero, Marco Cavallari, Pierre Stallforth, Peter H. Seeberger |
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| Rok vydání: | 2014 |
| Předmět: |
Time Factors
Carbohydrates Antigen-Presenting Cells HL-60 Cells Biology medicine.disease_cause Cell Line Microbiology Pneumococcal Vaccines Mice Antigen Immunity Conjugate vaccine Streptococcus pneumoniae medicine Animals Humans Molecular Biology Mice Knockout B-Lymphocytes Mice Inbred BALB C Vaccines Synthetic Immunization Passive Antibodies Monoclonal Germinal center Cell Biology Germinal Center Lipids Mice Inbred C57BL Vaccination Kinetics Immunization Immunology biology.protein Natural Killer T-Cells Antigens CD1d Antibody Immunologic Memory |
| Zdroj: | Nature Chemical Biology. 10:950-956 |
| ISSN: | 1552-4469 1552-4450 |
| DOI: | 10.1038/nchembio.1650 |
| Popis: | Severe forms of pneumococcal meningitis, bacteraemia and pneumonia result in more than 1 million deaths each year despite the widespread introduction of carbohydrate-protein conjugate vaccines against Streptococcus pneumoniae. Here we describe a new and highly efficient antipneumococcal vaccine design based on synthetic conjugation of S. pneumoniae capsule polysaccharides to the potent lipid antigen α-galactosylceramide, which stimulates invariant natural killer T (iNKT) cells when presented by the nonpolymorphic antigen-presenting molecule CD1d. Mice injected with the new lipid-carbohydrate conjugate vaccine produced high-affinity IgG antibodies specific for pneumococcal polysaccharides. Vaccination stimulated germinal center formation; accumulation of iNKT cells with a T follicular helper cell phenotype; and increased frequency of carbohydrate-specific, long-lived memory B cells and plasmablasts. This new lipid-carbohydrate vaccination strategy induced potent antipolysaccharide immunity that protected against pneumococcal disease in mice and may also prove effective for the design of carbohydrate-based vaccines against other major bacterial pathogens. |
| Databáze: | OpenAIRE |
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