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Immunization with R Mutants of S. Minnesota

I. Protection Against Challenge with Heterologous Gram-Negative Bacilli¹

Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, Boston, Massachusetts

Abstract

Recent studies have demonstrated that the basal core structure of the lipopolysaccharides of most Gram-negative bacilli are of similar or identical chemical structure. The current investigations evaluate the protective effect of immunization with these shared antigens against challenge with two heterologous Gram-negative bacilli, K. pneumoniae and E. coli 107. Active and passive immunization of mice with the Ra, Rb, Rc and Rd₁ mutants of S. minnesota failed to protect against challenge with K. pneumoniae. In contrast, active and passive immunization with the Rd₂ and Re mutants of S. minnesota afforded significant protection against challenge with K. pneumoniae. Similarly, active immunization with Re and passive immunization with Ra, Rc, Rd₂ and Re provided significant protection against challenge with E. coli 107. In all instances, immunization with Re afforded greater protection than any of the other rough mutants of S. minnesota. Active immunization with the Re mutant was considerably less effective than type specific immunization. Immunization with Re increased the LD₅₀ of E. coli 107 by 10-fold and K. pneumoniae by 100-fold over that of controls, while type specific immunization increased the LD₅₀ to these organisms by greater than 100-fold and 10,000-fold respectively. The specificity of the protection induced was demonstrated by the loss of the protective activity of rabbit antiserum to Re after adsorption of the serum with dead Re mutants.

Footnotes

¹ This study was supported by United States Public Health Service Research Grant AI 09584-02 and United States Public Health Service Training Grant 5 T01-AI-213-10.

² Professor of Medicine and Director of the Division of Infectious Diseases, University Hospital, Boston University School of Medicine, Boston, Massachusetts.