Similarities and disparities between core-specific and O-side-chain-specific antilipopolysaccharide monoclonal antibodies in models of endotoxemia and bacteremia in mice.
We have previously described cross-reactive antilipopolysaccharide (anti-LPS), or anti-endotoxin, monoclonal antibodies (MAbs) which provide cross-protection in several systems of endotoxin bioactivity. The protective effects of the murine cross-reactive MAb WN1 222-5 (immunoglobulin G2a(kappa) [IgG/2a(kappa)]) and of its chimerized version, SDZ 219-800 [human IgG1(kappa)], have now been evaluated in lethality models against LPS from three different serotypes and in bacterial infection models. We confirmed the protective activity of the two MAbs in D-galactosamine-sensitized mice challenged with LPS of other E. coli serotypes (O18, O127, and O111). The protective effect correlated with the suppression of tumor necrosis factor formation. Furthermore, WN1 222-5 enhanced bacterial clearance of intravenously administered E. coli O111 bacteria, thus protecting mice from death. However, the MAbs were unable to provide protection in a peritonitis model (intraperitoneal inoculation). Our study, therefore, shows that LPS cross-reactive antibodies are capable of mediating cross-protection against LPS and bacteria but that the selected models have a clear influence on the results.
Bailat
S
S
Division of Infectious Diseases, CHUV, Lausanne, Switzerland.
Heumann
D
D
Le Roy
D
D
Baumgartner
J D
JD
Rietschel
E T
ET
Glauser
M P
MP
Di Padova
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000918:Antibody Specificity; D016470:Bacteremia / Q000276:immunology*; D003429:Cross Reactions; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology; D005260:Female; D005688:Galactosamine / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology*; D051379:Mice
D000911:Antibodies, Monoclonal; D000939:Epitopes; D008070:Lipopolysaccharides; D005688:Galactosamine