1421767-98-7Relevant academic research and scientific papers
Automated glycan assembly of branched β-(1,3)-glucans to identify antibody epitopes
Weishaupt,Hahm,Geissner,Seeberger
, p. 3591 - 3594 (2017/03/31)
β-(1,3)-Glucans exhibit immunomodulatory and anti-tumor effects. Since the isolation of pure β-(1,3)-glucan oligosaccharides from natural sources is complicated, especially when certain branching patterns are desired, chemical synthesis is frequently the
Automated glycan assembly of a s. pneumoniae serotype 3 cps antigen
Weishaupt, Markus W.,Matthies, Stefan,Hurevich, Mattan,Pereira, Claney L.,Hahm, Heung Sik,Seeberger, Peter H.
supporting information, p. 1440 - 1446 (2016/08/02)
Vaccines against S. pneumoniae, one of the most prevalent bacterial infections causing severe disease, rely on isolated capsular polysaccharide (CPS) that are conjugated to proteins. Such isolates contain a heterogeneous oligosaccharide mixture of differe
Immunological evaluation of a synthetic clostridium difficile oligosaccharide conjugate vaccine candidate and identification of a minimal epitope
Martin, Christopher E.,Broecker, Felix,Oberli, Matthias A.,Komor, Julia,Mattner, Jochen,Anish, Chakkumkal,Seeberger, Peter H.
supporting information, p. 9713 - 9722 (2013/07/26)
Clostridium difficile is the cause of emerging nosocomial infections that result in abundant morbidity and mortality worldwide. Thus, the development of a vaccine to kill the bacteria to prevent this disease is highly desirable. Several recently identified bacterial surface glycans, such as PS-I and PS-II, are promising vaccine candidates to preclude C. difficile infection. To circumvent difficulties with the generation of natural PS-I due to its low expression levels in bacterial cultures, improved chemical synthesis protocols for the pentasaccharide repeating unit of PS-I and oligosaccharide substructures were utilized to produce large quantities of well-defined PS-I related glycans. The analysis of stool and serum samples obtained from C. difficile patients using glycan microarrays of synthetic oligosaccharide epitopes revealed humoral immune responses to the PS-I related glycan epitopes. Two different vaccine candidates were evaluated in the mouse model. A synthetic PS-I repeating unit CRM197 conjugate was immunogenic in mice and induced immunoglobulin class switching as well as affinity maturation. Microarray screening employing PS-I repeating unit substructures revealed the disaccharide Rha-(1→3)-Glc as a minimal epitope. A CRM197-Rha-(1→3)-Glc disaccharide conjugate was able to elicit antibodies recognizing the C. difficile PS-I pentasaccharide. We herein demonstrate that glycan microarrays exposing defined oligosaccharide epitopes help to determine the minimal immunogenic epitopes of complex oligosaccharide antigens. The synthetic PS-I pentasaccharide repeating unit as well as the Rha-(1→3)-Glc disaccharide are promising novel vaccine candidates against C. difficile that are currently in preclinical evaluation.
OLIGOSACCHARIDES AND OLIGOSACCHARIDE-PROTEIN CONJUGATES DERIVED FROM CLOSTRIDIUM DIFFICILE POLYSACCARIDE PS-I, METHODS OF SYNTHESIS AND USES THEREOF, IN PARTICULAR AS VACCINES AND DIAGNOSTIC TOOLS
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, (2013/03/26)
The invention relates to a synthetic oligosaccharide representing part of the repeating unit of the Clostridium difficile glycopolymer PS-I and having the sequence of the pentasaccharide a-L-Rhap- ( 1→3 ) -β-D-Glcp- ( 1→4 ) - [a-L-Rhap- ( 1→3 ] -a-D-Glcp- ( 1→2 ) -a-D-Glcp or a synthetic fragment or derivative thereof. Preferably, the claimed synthetic oligosaccharide bears at least one linker L for conjugation to a carrier protein or for immobilization on a surface. Further aspects of the invention relate to advantageous methods for synthesizing said synthetic oligosaccharide and oligosaccharide-protein conjugate as well as to uses thereof, in particular as vaccines and diagnostic tools.
