Live-Attenuated Salmonella Vaccine

Background

Salmonella enterica has been linked to the majority of foodborne outbreaks within the USA. The CDC estimates about 1.35 million Salmonella infections, 26,500 hospitalizations, and 420 deaths per year in the USA alone. The symptoms of Salmonella infections range from self-limiting gastroenteritis to sepsis and death, unless treated with antibiotics, and unfortunately the antibiotic resistance among Salmonella infections is a serious challenge to public health.

Salmonella contamination is often due to poultry since 1 out of 8 chickens is infected. Since the 1990s, there have been 45 outbreaks of salmonellosis linked to poultry, and in 2010, one of the biggest and most high-profile poultry related outbreaks involving 11 states led to ≈1939 illnesses and the recall of 380 million eggs. Collectively, Salmonella has a significant economic impact on poultry producers, as well as, a significant economic and medical impact on consumers. Therefore, a vaccine to prevent infection in farm animal populations or to protect humans directly is a critical need. Also, vaccines are known to mitigate the infection by antibiotic resistant pathogenic bacteria.

Although much effort has been devoted to developing vaccines against typhoidal serovars of Salmonella, currently there is no non-typhoidal Salmonella (NTS) vaccine available.

Technology Overview

Researchers in North Carolina State University’s Prestage Department of Poultry Science have developed a live‑attenuated strain of Salmonella enterica serovar typhimurium (NC983) for a NTS vaccine. The NC983 strain is a result from knockout mutations in the virulent S. Typhimurium background (American Type Culture Collection strain, ATCC 14028s). To test the immunogenicity of NC983, the vaccine strain was orally administered to mice, and an anti‑Salmonella antibody response was observed in vaccinated mice from two different genetic backgrounds. Mice that were vaccinated survived two escalating challenges with a wild-type virulent strain of Salmonella (see ). In a study with chickens, preliminary data showed that the NC983 vaccine triggers the expression of different immune response genes compared to commercially available Salmonella vaccines. Therefore, this vaccine has the potential to offer additional protection.

Click here to view the published journal article titled “Attenuated Salmonella enterica Serovar Typhimurium, Strain NC983, Is Immunogenic, and Protective against Virulent Typhimurium Challenges in Mice”

Benefits

• Protection from non-typhoidal Salmonella infections
• More robust immune response compared to heat‑inactivated or conjugate vaccines
• Deletion of multiple genes leads to total attenuation with minimal probability of reversion to virulence

Applications

• Livestock vaccine
• Human vaccine (needs further development)
• Protection against gastroenteritis and extra‑intestinal invasive bacteremia Salmonella infection

Opportunity

NC State University is seeking an industry partner to develop and commercialize this technology.