title: Prevention of Staphylococcus aureus infections by glycoprotein vaccines synthesized in Escherichia coli.
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 α 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.
authors.affiliation: GlycoVaxyn, Schlieren, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Wacker
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Kowarik
authors.forename: Meghan
authors.initials: M
authors.lastname: Dowd
authors.forename: Gerd
authors.initials: G
authors.lastname: Lipowsky
authors.forename: Amir
authors.initials: A
authors.lastname: Faridmoayer
authors.forename: Kelly
authors.initials: K
authors.lastname: Shields
authors.forename: Saeyoung
authors.initials: S
authors.lastname: Park
authors.forename: Cristina
authors.initials: C
authors.lastname: Alaimo
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Kelley
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Julien
authors.initials: J
authors.lastname: Quebatte
authors.forename: Veronica
authors.initials: V
authors.lastname: Gambillara
authors.forename: Paula
authors.initials: P
authors.lastname: Carranza
authors.forename: Michael
authors.initials: M
authors.lastname: Steffen
authors.forename: Jean C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006001:Glycoconjugates / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D014614:Vaccines, Synthetic
chemical_list: D001426:Bacterial Proteins; D006001:Glycoconjugates; D006023:Glycoproteins; D013209:Staphylococcal Vaccines; D014614:Vaccines, Synthetic
keywords: Staphylococcus aureus; animal infection models; bacteremia; bioconjugate vaccine; capsular polysaccharides; glycoengineering; glycoprotein; pneumonia