Cross-reactive antigens: their potential for immunization-induced immunity to Gram-negative bacteria

The involvement of multiple species and serologic types in gram-negative bacteremia prompted evaluation of immunization with shared, cross-reactive antigens of gram negative bacilli. Active and passive immunization with Re chemotype mutants of Salmonella minnesota afforded significant protection against heterologous gram-negative bacilli and were considerably more effective than immunization with smooth S. minnesota or its Ra, Rb, Rc, Rd1 and Rd2 mutants. Since the lipopolysaccharide of the Re mutant is composed solely of 2-keto-3-deoxycotonate (KDO) and lipid A, the protective activity of antibody to the Re mutant and lipid A was evaluated. Immunization with Re mutant protected granulocytopenic rabbits against lethal bacteremia and protected mice against lethal challenge with heterologous endotoxins, whereas antibody to lipid A had no protective activity. In concomitant clinical studies, high titers of antibody to the Re mutant at the onset of bacteremia were associated with a significant diminution in the frequency of shock and death, which was independent of any effect of O-specific antibody.