Immunogenicity of Irradiated Salmonella Typhimurium Cells and Endotoxin

The effects of high doses of radiation (1, 5, or 20 Mrad) on the toxicity, pyrogenicity, and immunogenicity of Salmonella typhimurium cells and endotoxin were studied. Toxicity decreased progressively after exposure to 1, 5, or 20 Mrad. The lethal effect of 1-Mrad exposed cells was greater than that of heat-, acetone-, or alcohol-killed preparations. An amount of 5 Mrad is about a 50% end point in terms of inactivation of the lethal lipopolysaccharide or cell-associated determinants. The fever response to radiation-killed salmonellae decreased between 1- and 20-Mrad exposure. The immunogenicity of 1-Mrad-treated cells usually exceeded that of nonirradiated preparations in mouse-protection tests. With increasing radiation doses, there was a dramatic decrease in, but not an abolition of, immunogenicity. Preparations exposed to 20 Mrad which were nonlethal afforded significant protection. The results are interpreted as a reflection of a dissociation of the primary and secondary toxic determinants of endotoxin after irradiation. The data indicate the potential value of radiation sterilization as a means of production of Salmonella vaccine.