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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Van Haperen, Rien Saleh, Maher De Boer, Ernie Chen, Tao Drabek, Dubravka Bourcier, Tristan Subilia, Audrey Grosveld, Frank Prévost, Gilles Rademaker, Hendrik Jan Janssens, Rick Laventie, Benoît-joseph Marcellin, Luc Lebbink, Joyce H. G. |
| Description | Author Affiliation: Laventie BJ ( Faculté de Médecine, Physiopathologie et Médecine Translationnelle, Institut de Bactériologie, Centre Hospitalier Régional Universitaire, Université de Strasbourg, 67000 Strasbourg, France.); |
| Abstract | Panton-Valentine leukocidin (PVL) is a pore-forming toxin associated with current outbreaks of community-associated methicillin-resistant strains and implicated directly in the pathophysiology of Staphylococcus aureus-related diseases. Humanized heavy chain-only antibodies (HCAb) were generated against S. aureus PVL from immunized transgenic mice to neutralize toxin activity. The active form of PVL consists of the two components, LukS-PV and LukF-PV, which induce osmotic lysis following pore formation in host defense cells. One anti-LukS-PV HCAb, three anti-LukF-PV HCAbs with affinities in the nanomolar range, and one engineered tetravalent bispecific HCAb were tested in vitro and in vivo, and all prevented toxin binding and pore formation. Anti-LukS-PV HCAb also binds to γ-hemolysin C (HlgC) and inhibits HlgC/HlgB pore formation. Experiments in vivo in a toxin-induced rabbit endophthalmitis model showed that these HCAbs inhibit inflammatory reactions and tissue destruction, with the tetravalent bispecific HCAb performing best. Our findings show the therapeutic potential of HCAbs, and in particular, bispecific antibodies. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 39 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibodies, Bispecific Immunology Antibodies, Neutralizing Exotoxins Immunoglobulin Heavy Chains Staphylococcus Aureus Metabolism Amino Acid Sequence Animals Chemistry Antibody Affinity Antibody Specificity Enzyme-Linked Immunosorbent Assay Molecular Sequence Data Rabbits Sequence Homology, Amino Acid Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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