Oral immunization with live, avirulent fla+ strains of Salmonella protects mice against subsequent oral challenge with Salmonella typhimurium.

Some strains of Salmonella, when fed to mice, establish a nonlethal, limited infection in the Peyer's patches of the small intestine. When such mice are later challenged orally with a normally lethal dose of virulent Salmonella typhimurium, a protective effect of the prior vaccination is seen. In an effort to characterize the determinant(s) of the avirulent strains responsible for this protective effect, we examined the cell envelope protein profiles of five such protective strains and of eight strains of Salmonella that were both nonpersistent and nonprotective when fed to mice. The protective strains produced high levels of flagellin. We made otherwise isogenic fla+ and fla- derivatives of two such strains and showed that although the fla- derivatives colonized mice as well as did the fla+ strains, the fla- derivatives given orally showed a much reduced ability to protect mice from S. typhimurium challenge. Both fla+ and fla- strains induced cellular immunity in vaccinated mice.