Human monoclonal antibodies to Pseudomonas aeruginosa alginate that protect against infection by both mucoid and nonmucoid strains.
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.
Pier
Gerald B
GB
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. gpier@channing.harvard.edu
Boyer
Debra
D
Preston
Michael
M
Coleman
Fadie T
FT
Llosa
Nicolas
N
Mueschenborn-Koglin
Simone
S
Theilacker
Christian
C
Goldenberg
Hannah
H
Uchin
Jeffrey
J
Priebe
Gregory P
GP
Grout
Martha
M
Posner
Marshall
M
Cavacini
Lisa
L
D000208:Acute Disease; D000464:Alginates / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001666:Binding Sites, Antibody; D004195:Disease Models, Animal; D005260:Female; D020723:Glucuronic Acid / Q000276:immunology* / Q000378:metabolism; D006603:Hexuronic Acids / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism; D013045:Species Specificity
D000464:Alginates; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D006603:Hexuronic Acids; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins; D020723:Glucuronic Acid