Monoclonal antibodies to salmonella lipopolysaccharide: functional analysis of anti-lipid A antibodies.

We have produced monoclonal antibodies (MoAb) to the Rb core and lipid A regions of Salmonella lipopolysaccharide (LPS) and have assessed their ability to inhibit LPS-mediated mitogenic responses in vitro, and to protect against LPS toxicity and lethal Salmonella infection in vivo. Monoclonal antibodies RC-8 and RC-16 were specific for LPS Rb core determinants, and MoAb LA-1, LA-2, LA-3, LA-4 and LA-5 were specific for lipid A. Anti-lipid A MoAb LA-2, LA-3 and LA-5 were found to abrogate mitogenic responses of C3H/HeN spleen cells to smooth S. typhimurium LPS (S LPS) and to rough S. minnesota R595 LPS (Re LPS). Monoclonal antibody LA-5 was effective in extending the median length of survival of C3H/HeN mice challenged with a lethal dose of either S LPS or Re LPS. Antibody LA-2 could extend the median length of survival of C3H/HeJ mice challenged with Re LPS but not with S LPS, and failed to extend significantly the length of survival of S LPS-challenged C3H/HeN and DBA/2 mice. Neither 20 micrograms of anti-Rb core or anti-lipid A MoAb nor 200 micrograms of anti-lipid A MoAb were able to protect C3H/HeN or BALB/c mice, respectively, against lethal infection with S. typhimurium SR-11. These results suggest that the importance of anti-lipid A antibodies in host defence may lie more in their ability to neutralize pathological effects of LPS, than in their ability to protect against bacterial infection.