Abstract
ABSTRACTStrep A is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. RhaPS is a validated universal vaccine candidate in a glycoconjugate prepared by chemical conjugation of the native carbohydrate to a carrier protein. We engineered the Group A Carbohydratte biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins withinE. colicells. The structural integrity of the produced recombinant glycoconjugate vaccines was confirmed by NMR spectroscopy and mass spectrometry. Purified RhaPS glycoconjugates elicited carbohydrate-specific antibodies in mice and rabbits and bound to the surface of multiple Strep A strains of diverse M-types, confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates.
Publisher
Cold Spring Harbor Laboratory
Reference80 articles.
1. Sims Sanyahumbi, A. , et al., Global Disease Burden of Group A Streptococcus, in Streptococcus pyogenes : Basic Biology to Clinical Manifestations, J.J. Ferretti , D.L. Stevens , and V.A. Fischetti , Editors. 2016: Oklahoma City (OK).
2. How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease
3. Di Benedetto, R. , et al., Rational Design of a Glycoconjugate Vaccine against Group A Streptococcus. Int J Mol Sci, 2020. 21(22).
4. Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate
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