Salmonella expressing detoxified lipopolysaccharide is immunogenic and protective both as an attenuated vaccine and for delivery of foreign antigens.

The construction of safe and protective vaccines, derived from human pathogens that have been genetically modified to remove pathogenicity, is often easier to accomplish on paper than it is in the laboratory. Kong and colleagues have pursued a clever strategy to reduce the reactogenicity of attenuated Salmonella oral vaccines by genetically modifying the surface lipopolysaccharide to lower endotoxic activity. The resulting candidate vaccine strains were highly reduced in virulence yet were able to confer protection in a mouse model against challenge with virulent Salmonella. Remarkably, these strains could also be further modified to present foreign antigens from unrelated human pathogens and again confer protection against heterologous challenge. This work brings important new tools to bear on solving the problem of creating efficacious attenuated bacterial vaccines that maximize both safety and immunogenicity in clinical trials.