In the past, we showed that the pyrogenicity of meningococcal LOS in rabbits was reduced at least 100-fold if it was tightly associated with outer-membrane proteins (OMP). In contrast, the immunostimulatory effects of OMP-associated LOS remained strong. Immunization of mice with the OMP-associated LOS protected them against experimental meningococcal infection and septic shock. We plan to further reduce the pyrogenicity and other toxicity of the OMP-associated LOS by removal of O-acyl groups from lipid A by generating meningococcal mutants with de-O-acylated lipid A genetically. We have cloned meningococcal htrB2 gene, which encodes an O-acyl transferase, into E. coli. Once we obtain the mutant of Neisseria meningitidis with de-O-acylated lipid A, we will investigate the toxicity and beneficial immunostimulatory effects of genetically detoxified meningococcal LOS and its OMP-associated LOS.
