ANTIIDIOTYPIC IMMUNIZATION PROVIDES PROTECTION AGAINST LETHAL ENDOTOXEMIA IN BALB C MICE/

Against lipid A (the conserved moiety of lipopolysaccharides from Gram -negative bacteria) neutralizing IgM monoclonal antibodies (mAb) 8-2 a nd 26-20 anti-idiotypic (Ab2) mAb were produced: Ab2 mAb KM-04 (IgG1) against mAb8-2, and Ab2 mAb PW-1 (IgG2a) and PW-2 (IgG1) against mAb 2 6-20. The binding of Ab2 mAb KM-04 to 8-2 (Ab1) was strongly inhibited by a lipopolysaccharide (LPS) extract from either Salmonella minnesot a R595 (Re LPS) or Escherichia coli J5 (Rc LPS), whereas the binding o f Ab2 mAb PW-1 and PW-2 to 26-20 (Ab 1) was only marginally inhibited by both Re LPS and Rc LPS. The results indicated that Ab2 mAb KM-04 re cognizes a lipid A-binding site related idiotope on mAb 8-2 and theref ore KM-04 might bear the internal image of a neutralization determinin g epitope of lipid A. Consequently Ab2 KM-04 might induce antibodies t o lipid A. Indeed anti-idiotypic immunization of syngeneic BALB/c mice with Ab2 mAb KM-04 resulted in development of lipid A-binding anti-an ti-idiotypic (Ab3) antibodies in serum. Similar immunizations with Ab2 mAb PW-1 and PW-2 were unsuccessful. However, induction of lipid A-bi nding Ab3 by mAb KM-04 proved to be genetically restricted to BALB/c m ice. DBA/2 mice, Swiss mice and rabbits did not develop lipid A-bindin g antibodies upon immunization with mAb KM-04. In protection experimen ts, it was shown that BALB/c mice vaccinated with mAb KM-04 showed sig nificantly enhanced survival from challenge with either rough (Re) LPS from Salmonella minnesota or smooth LPS from E. coli 0111:B4 when com pared to BALB/c mice immunized with a non-relevant Ab2 mAb. The result s suggest that mAb KM-04 constitutes a non-internal image vaccine to t he lethal effect of lipid A in BALB/c mice. Furthermore an Ab3 mAb was prepared against Ab2 mAb KM-04 that showed reactivity with Re LPS. Th is Ab3 mAb, designated LE-21 (IgG2a) protected mice against an otherwi se lethal challenge of Re LPS.