Characterization of the opsonic and protective activity against Staphylococcus aureus of fully human monoclonal antibodies specific for the bacterial surface polysaccharide poly-N-acetylglucosamine.

Infection and Immunity
Casie Kelly-QuintosGerald B Pier

Abstract

Carbohydrate antigens are important targets of the immune system in clearing bacterial pathogens. Although the immune system almost exclusively uses antibodies in response to foreign carbohydrates, there is still much to learn about the role of different epitopes on the carbohydrate as targets of protective immunity. We examined the role of acetyl group-dependent and -independent epitopes on the staphylococcal surface of polysaccharide poly-N-acetylated glucosamine (PNAG) by use of human monoclonal antibodies (MAbs) specific for such epitopes. We utilized hybridoma technology to produce fully human immunoglobulin G2 (IgG2) MAbs from B cells of an individual post-Staphylococcus aureus infection and cloned the antibody variable regions to produce an IgG1 form of each original MAb. Specificity and functionality of the purified MAbs were tested in vitro using enzyme-linked immunosorbent assays, complement deposition, and opsonophagocytic assays. We found that a MAb (MAb F598) that bound the best to nonacetylated or backbone epitopes on PNAG had superior complement deposition and opsonophagocytic activity compared to two MAbs that bound optimally to PNAG that was expressed with a native level (>90%) of N-acetyl groups (MAbs F628 and...Continue Reading

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Citations

Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Pauline Yoong, Gerald B Pier
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Colette Cywes-BentleyGerald B Pier
Aug 18, 2012·The Journal of Antimicrobial Chemotherapy·Damien RouxDavid Skurnik
Jun 26, 2007·Journal of Bacteriology·Gina Parise SloanRajendar Deora
Nov 23, 2006·Journal of Bacteriology·Gina PariseRajendar Deora
Aug 27, 2010·The Journal of Clinical Investigation·Liise-Anne Pirofski
Jun 20, 2013·International Journal of Biological Sciences·Angela FrançaGerald B Pier
Nov 29, 2007·Future Microbiology·Knut Ohlsen, Udo Lorenz
Apr 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nuno CercaGerald B Pier
Jun 25, 2014·Expert Review of Vaccines·Maria Dolores MoraguesGuillermo Quindos
Nov 5, 2015·Expert Opinion on Investigational Drugs·Cuong VuongMichael Otto
Jul 9, 2013·Expert Opinion on Drug Discovery·Michio KurosuKatsuhiko Mitachi
Feb 13, 2016·Frontiers in Microbiology·Alena JandaArturo Casadevall
Nov 21, 2015·Pathogens and Disease·Natalia CattelanRajendar Deora
Jan 10, 2016·The Journal of Antimicrobial Chemotherapy·David SkurnikGerald B Pier
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Jun 26, 2013·Human Vaccines & Immunotherapeutics·Gerald B Pier
Dec 4, 2014·International Journal of Medical Microbiology : IJMM·Sanne van den BergIrma A J M Bakker-Woudenberg
Feb 26, 2015·Frontiers in Cellular and Infection Microbiology·Carla Renata ArciolaLucio Montanaro
Oct 14, 2014·Frontiers in Immunology·Kok P M van KesselJos A G van Strijp
Jul 10, 2019·Infection and Immunity·Ermioni KalfopoulouJohannes Huebner
May 31, 2018·Investigative Ophthalmology & Visual Science·Tanweer S ZaidiGerald B Pier
Jul 3, 2016·Immunogenetics·Catherine M Crosby, Mitchell Kronenberg

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