Prevention of Staphylococcus aureus Infections by Glycoprotein Vaccines Synthesized in Escherichia coli
| Autor: | Michael Wacker, Linhui Wang, Michael Kowarik, Meghan Dowd, Gerd Lipowsky, Amir Faridmoayer, Kelly Shields, Saeyoung Park, Cristina Alaimo, Kathryn A. Kelley, Martin Braun, Julien Quebatte, Veronica Gambillara, Paula Carranza, Michael Steffen, Jean C. Lee |
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| Rok vydání: | 2013 |
| Předmět: |
Staphylococcus aureus
Glycoconjugate chemical and pharmacologic phenomena medicine.disease_cause Staphylococcal infections complex mixtures Microbiology Mice Major Articles and Brief Reports Bacterial Proteins Escherichia coli medicine Animals Humans Immunology and Allergy Glycoproteins chemistry.chemical_classification Vaccines Synthetic biology Staphylococcal Vaccines Gene Expression Regulation Bacterial Staphylococcal Infections medicine.disease Virology Infectious Diseases Immunization chemistry Bacteremia biology.protein Rabbits Antibody Glycoprotein Glycoconjugates |
| Zdroj: | The Journal of Infectious Diseases. 209:1551-1561 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jit800 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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