A Live Oral Fowl Typhoid Vaccine with Reversible O-Antigen Production

Salmonella enterica serovar Gallinarum causes fowl typhoid, recognized worldwide as an economically important disease. The current vaccine, 9R, lacks a complete O antigen, which is a Salmonella virulence factor, and, in addition, has a number of other less well characterized chromosomal mutations. For optimal efficacy, 9R is administered by injection. In an effort to develop a vaccine suitable for oral administration, we constructed Salmonella Gallinarum strains with a reversible O-antigen phenotype. In this scenario, the vaccine strain produces full-length O antigen at the time it is administered to birds. After the vaccine has had time to colonize internal lymphoid tissues, the O-antigen is gradually lost, resulting in an attenuated strain. We found that strains carrying single mutations conferring this phenotype, Apmi and arabinose-regulated rfc, retained virulence. However, a mutant strain carrying both of these mutations was completely attenuated and immunogenic in chickens. This work demonstrates a novel approach for developing live Salmonella vaccines for poultry.