Salmonella DNA adenine methylase mutants elicit early and late onset protective immune responses in calves.

Salmonellosis is an important disease of livestock and Salmonella contamination of livestock-derived food products and effluents pose a significant risk to human health. Salmonella vaccines currently available to prevent salmonellosis in cattle have limited efficacy. Here we evaluated a Salmonella enterica serovar Typhimurium vaccine strain lacking the DNA adenine methylase (Dam) for safety and efficacy in calves. Vaccination was safe in calves, and following challenge with virulent Typhimurium 4 weeks post-immunization, vaccinated animals exhibited significantly lower mortality, diarrhea, and rectal temperatures, as well as reduced colonization of gastrointestinal tract and visceral organs compared to non-vaccinated control animals. Additionally, early onset protection (competitive exclusion) in vaccinated neonatal calves was demonstrated by attenuated clinical disease (as measured by rectal temperatures and attitude scores) and reduced mortality when challenged with virulent Typhimurium 24h after immunization. Taken together, these data suggest that vaccination with Salmonella Dam mutant strains confer significant protection against Salmonella infections in cattle via both adaptive immunity and competitive exclusion mechanisms.