dc.contributor.author
Seco, Bruna M. S.
dc.contributor.author
Xu, Fei-Fei
dc.contributor.author
Grafmüller, Andrea
dc.contributor.author
Kottari, Naresh
dc.contributor.author
Pereira, Claney L.
dc.contributor.author
Seeberger, Peter H.
dc.date.accessioned
2020-11-19T14:29:28Z
dc.date.available
2020-11-19T14:29:28Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/28912
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-28661
dc.description.abstract
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.
en
dc.format.extent
11 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
conjugate vaccines
en
dc.subject
immune-response
en
dc.subject
pathogenesis
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
Sequential Linkage of Carbohydrate Antigens to Mimic Capsular Polysaccharides: Toward Semisynthetic Glycoconjugate Vaccine Candidates against Streptococcus pneumoniae Serotype 14
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1021/acschembio.0c00360
dcterms.bibliographicCitation.journaltitle
ACS Chemical Biology
dcterms.bibliographicCitation.number
9
dcterms.bibliographicCitation.pagestart
2395
dcterms.bibliographicCitation.pageend
2405
dcterms.bibliographicCitation.volume
15
dcterms.bibliographicCitation.url
https://doi.org/10.1021/acschembio.0c00360
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
1554-8929
dcterms.isPartOf.eissn
1554-8937
refubium.resourceType.provider
WoS-Alert