Ontology highlight
ABSTRACT: Background
Staphylococcus aureus is a leading cause of superficial and invasive human disease that is often refractory to antimicrobial therapy. Vaccines have the potential to reduce the morbidity, mortality, and economic impact associated with staphylococcal infections. However, single-component vaccines targeting S. aureus have failed to show efficacy in clinical trials.Methods
A novel glycoengineering technology for creation of a multicomponent staphylococcal vaccine is described. Genes encoding S. aureus capsular polysaccharide (CP) biosynthesis, PglB (a Campylobacter oligosaccharyl transferase), and a protein carrier (detoxified Pseudomonas aeruginosa exoprotein A or S. aureus ? toxin [Hla]) were coexpressed in Escherichia coli. Recombinant proteins N-glycosylated with S. aureus serotype 5 or 8 CPs were purified from E. coli.Results
Rabbits and mice immunized with the glycoprotein vaccines produced antibodies that were active in vitro in functional assays. Active and passive immunization strategies targeting the CPs protected mice against bacteremia, and vaccines targeting Hla protected against lethal pneumonia. The CP-Hla bioconjugate vaccine protected against both bacteremia and lethal pneumonia, providing broad-spectrum efficacy against staphylococcal invasive disease.Conclusions
Glycoengineering technology, whereby polysaccharide and protein antigens are enzymatically linked in a simple E. coli production system, has broad applicability for use in vaccine development against encapsulated microbial pathogens.
SUBMITTER: Wacker M
PROVIDER: S-EPMC3997581 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
Wacker Michael M Wang Linhui L Kowarik Michael M Dowd Meghan M Lipowsky Gerd G Faridmoayer Amir A Shields Kelly K Park Saeyoung S Alaimo Cristina C Kelley Kathryn A KA Braun Martin M Quebatte Julien J Gambillara Veronica V Carranza Paula P Steffen Michael M Lee Jean C JC
The Journal of infectious diseases 20131205 10
<h4>Background</h4>Staphylococcus aureus is a leading cause of superficial and invasive human disease that is often refractory to antimicrobial therapy. Vaccines have the potential to reduce the morbidity, mortality, and economic impact associated with staphylococcal infections. However, single-component vaccines targeting S. aureus have failed to show efficacy in clinical trials.<h4>Methods</h4>A novel glycoengineering technology for creation of a multicomponent staphylococcal vaccine is descri ...[more]