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The Journal of Immunology, 2004, 173: 5671-5678.
Copyright © 2004 by The American Association of Immunologists

Human Monoclonal Antibodies to Pseudomonas aeruginosa Alginate That Protect against Infection by Both Mucoid and Nonmucoid Strains1

Gerald B. Pier2,*, Debra Boyer*,{dagger}, Michael Preston*, Fadie T. Coleman*, Nicolas Llosa*, Simone Mueschenborn-Koglin*, Christian Theilacker3,*, Hannah Goldenberg4,*, Jeffrey Uchin*, Gregory P. Priebe*,{ddagger}, Martha Grout*, Marshall Posner§ and Lisa Cavacini§

* Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Divisions of {dagger} Pulmonary Medicine, and {ddagger} Infectious Diseases and Critical Care, Children’s Hospital Boston, and § Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115

Two fully human mAbs specific for epitopes dependent on intact carboxylate groups on the C6 carbon of the mannuronic acid components of Pseudomonas aeruginosa alginate were found to promote phagocytic killing of both mucoid and nonmucoid strains as well as protection against both types of strains in a mouse model of acute pneumonia. The specificity of the mAbs for alginate was determined by ELISA and killing assays. Some strains of P. aeruginosa did not make detectable alginate in vitro, but in vivo protection against lethal pneumonia was obtained and shown to be due to rapid induction of expression of alginate in the murine lung. No protection against strains genetically unable to make alginate was achieved. These mAbs have potential to be passive therapeutic reagents for all strains of P. aeruginosa and the results document that alginate is a target for the proper type of protective Ab even when expressed at low levels on phenotypically nonmucoid strains.




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