The capacity of
lipid A, a structure common to the
lipopolysaccharide cores of all gram-negative bacteria, to serve as an active immunizing agent in mice and to protect these animals against gram-negative
infections was investigated. Active immunization experiments were also performed with the Re mutant of Salmonella minnesota 595 which carries a
lipopolysaccharide composed of
lipid A and three residues of ketodeoxyoctonic
acid. Single
injections of
lipid A complexed to
acid-hydrolyzed bacteria as carriers failed to induce specific protection against subsequent challenge
infections with E. coli O4 and S. breslau. Repeated
injections of
lipid A resulted in good protection against intraperitoneal challenge with S. breslau and partial protection against intravenous challenge with the same organism but did not alter the sensitivity of mice to challenge
infections with E. coli or Pasteurella multocida. Whole
antisera or serum fractions from rabbits in which high titers against
lipid A had been attained by repeated
intravenous injections of the
antigen did not protect mice against challenge
infections with E. coli O4. In contrast a single injection of the Re mutant of S. minnesota
antigen in combination with
incomplete Freund's adjuvant provided substantial protection against an otherwise lethal intraperitoneal
infection with S. breslau over a period of at least 45 days. Repeated application of the Re
antigen resulted in partial protection against experimental
infections with E. coli O4, S. breslau and Pasteurella multocida.
Injections of S. minnesota Re 595 antiserum provided better protection against an E. coli O4
infection than
lipid A sera or
antibodies of the
IgG or
IgM type directed against this
antigen.