Revised structures for the capsular polysaccharides from Staphylococcus aureus Types 5 and 8, components of novel glycoconjugate vaccines

摘要

Glycoconjugate vaccines based on the capsular polysaccharides (CPSs) from Staphylococcus aureus serotypes 5 and 8 conjugated to genetically detoxified recombinant exoprotein A (rEPA) from Pseudomonas aeruginosa have been shown, in Phase 3 clinical trials, to elicit a strong bactericidal immune response in end-stage renal disease patients. Such vaccines have the potential to reduce morbidity and mortality due to methicillin-resistant Staphylococcus aureus (MRSA), a major cause of hospital-acquired infection. The serotype 5 and 8 polysaccharides have been fully characterized by NMR spectroscopy and full structural analyses carried out. Published structures were found incorrect and the revised structures of the repeat units of the two polysaccharides are:Type 5 -> 4)-beta-D-ManNAcA-(1 -> 4)-alpha-L-FucNAc(3OAc)(.)(1 -> 3)-beta-D-FucNAc-(1 ->Type 8 -> 3)-beta-D-ManNAcA(4OAc)-(1 -> 3)-alpha-L-FucNAc-(1 -> 3)-alpha-D-FucNAc-(1 ->Resonances indicative of the presence of peptidoglycan were observed in the spectra of both CPSs, consistent with reports that the CPS is covalently linked to peptidoglycan. (c) 2005 Elsevier Ltd. All rights reserved.