Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5

Glycoconjugate vaccines based on isolated capsular polysaccharide (CPS) save millions of lives annually by preventing invasive pneumococcal disease caused by Streptococcus pneumoniae. Some components of the S. pneumoniae glycoconjugate vaccine Prevnar13 that contains CPS antigens from 13 serotypes u...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-10, Vol.114 (42), p.11063-11068
Main Authors: Lisboa, Marilda P., Khan, Naeem, Martin, Christopher, Xu, Fei-Fei, Reppe, Katrin, Geissner, Andreas, Govinda, Subramanian, Witzenrath, Martin, Pereira, Claney L., Seeberger, Peter H.
Format: Article
Language:English
Subjects:
Analogs
Antigens
Avidity
Biological Sciences
Chemical modification
Conjugation
Epitopes
Glycoconjugates
Immune response
Immune system
Immunoglobulins
Immunological memory
Long term memory
Physical Sciences
Serotypes
Streptococcus infections
Streptococcus pneumoniae
Vaccines
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Summary:Glycoconjugate vaccines based on isolated capsular polysaccharide (CPS) save millions of lives annually by preventing invasive pneumococcal disease caused by Streptococcus pneumoniae. Some components of the S. pneumoniae glycoconjugate vaccine Prevnar13 that contains CPS antigens from 13 serotypes undergo modifications or degradation during isolation and conjugation, resulting in production problems and lower efficacy. We illustrate how stable, synthetic oligosaccharide analogs of labile CPS induce a specific protective immune response against native CPS using S. pneumoniae serotype 5 (ST-5), a problematic CPS component of Prevnar13. The rare aminosugar L-PneuNAc and a branched L-FucNAc present in the natural repeating unit (RU) are essential for antibody recognition and avidity. The epitope responsible for specificity differs from the part of the antigen that is stabilized by chemical modification. Glycoconjugates containing stable, monovalent synthetic oligosaccharide analogs of ST-5 CPS RU induced long-term memory and protective immune responses in rabbits superior to those elicited by the ST-5 CPS component in multivalent Prevnar13.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1706875114