Further characterization of monoclonal antibodies to lipopolysaccharide of Salmonella Minnesota strain R595.
We have shown here that despite the use of monoclonal antibodies with well-defined epitope-specificities, and despite testing them in the most simple animal model available (i.e., mixing of homologous LPS with Mab prior to injection), we are not yet able to explain why some of the antibodies were effective and others not. For some of the clones (e.g., clone 20), an even better definition of binding sites is currently taking place in an attempt to obtain this understanding. We also do not yet understand why clone 20 was not effective in the mucin model, while using much lower amounts of injected antibody, and much higher challenge doses, this Mab was effective against E. coli in the gentamicin-treated mouse model. Very clear is, however, that in order to be protective in the latter model, Mabs are not required to be specific for lipid A. In the future it will be essential to develop procedures which measure specific interaction between smooth LPS/bacteria and antibodies to the LPS core region. In addition, it will be of great help when the chemical structure of non-substituted, rough-form LPS, as occurring in smooth LPS preparations, would be defined. This applies also to O-substituted core molecules.
Appelmelk
B J
BJ
Department of Medical Microbiology, Vuije Universiteit, Amsterdam, The Netherlands.
Cohen
J
J
Silva
A
A
Verweij-van Vught
A M
AM
Brade
H
H
Maaskant
J J
JJ
Schouten
W F
WF
Mol
O
O
Honing
A
A
Thijs
L G
LG
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000276:immunology; D000918:Antibody Specificity; D003429:Cross Reactions; D004926:Escherichia coli / Q000276:immunology; D005839:Gentamicins / Q000494:pharmacology; D006454:Hemoglobins / Q000502:physiology; D007711:Klebsiella pneumoniae / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000633:toxicity; D009503:Neutropenia / Q000139:chemically induced / Q000276:immunology; D011112:Polymyxin B / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D012475:Salmonella / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D005839:Gentamicins; D006454:Hemoglobins; D008070:Lipopolysaccharides; D009077:Mucins; D011112:Polymyxin B