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Nat Chem Biol. 2014 Nov;10(11):950-6. doi: 10.1038/nchembio.1650. Epub 2014 Oct 5.

A semisynthetic carbohydrate-lipid vaccine that protects against S. pneumoniae in mice.

Author information

1
Experimental Immunology Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
2
Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
3
SAW Instruments, Bonn, Germany.
4
1] Experimental Immunology Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland. [2] SIgN (Singapore Immunology Network), A*STAR (Agency for Science, Technology and Research) Biopolis, Singapore.
5
Infection Biology, Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.

Abstract

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.

PMID:
25282505
DOI:
10.1038/nchembio.1650
[Indexed for MEDLINE]

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