Breakthrough in Designing a Better Salmonella Vaccine
Researchers at UC Davis have announced a major breakthrough in Salmonella vaccine development, identifying the specific immune cells that offer optimal protection against infection. The findings, published in the Proceedings of the National Academy of Sciences, bring scientists closer to a safer and more effective Salmonella vaccine — one capable of protecting the estimated one million people who die from the disease each year worldwide.
Professor Stephen McSorley, interim director of the Center for Comparative Medicine, led a collaborative team from the University of Melbourne, the University of Connecticut, and UC Davis. The group evaluated two categories of memory T cells — circulating and non-circulating — to determine which type provides stronger immunity against Salmonella infection in mouse models.
Two Types of T Cells Behind Salmonella Vaccine Immunity
For decades, immunology research has focused on antibody and general T cell responses when studying infectious diseases. However, a more recent discovery revealed that T cells are not a single uniform population. Some circulate through tissues across the body, while others — known as tissue resident or non-circulating memory T cells — remain fixed in specific locations and never migrate.
“What hasn’t been realized until very recently is there are actually two different categories of T cells,” said McSorley. “Those that circulate through tissues in the body and those that never move and are known as tissue resident or non-circulating memory cells.”
Since their discovery, non-circulating memory T cells have drawn significant attention across disease models — from cancer to infectious diseases — as researchers work to understand whether this cell population plays a meaningful protective role.
The Role of Liver Memory T Cells in Salmonella Protection
The UC Davis team focused specifically on Salmonella Typhi, a strain responsible for life threatening enteric fever that is most prevalent in parts of Africa and Asia. Other Salmonella strains cause gastroenteritis or invasive non-typhoidal Salmonellosis (NTS), an emerging and deadly disease in sub-Saharan Africa. Without access to medical care, enteric fever and NTS are fatal in 20 to 25 percent of infected individuals.
To test how well each T cell type protects against reinfection, the researchers transferred circulating and non-circulating memory T cells from previously vaccinated mice into unvaccinated mice. Using fluorescent markers, they tracked which cells provided effective protection.
The results were clear: vaccine mediated protection depends on a non-circulating population of liver memory T cells that do not migrate to other parts of the body. This unexpected finding redefines what future Salmonella vaccines must achieve — generating these liver resident memory T cells will be a foundational requirement for next generation typhoid and NTS vaccines.
Current Salmonella Vaccines Fall Short
NTS has become an increasingly serious public health concern in Africa over the past decade, particularly affecting young children, elderly individuals, and people living with HIV. In immunocompromised individuals, strains that would typically cause mild gastroenteritis can progress to systemic infection with fatal outcomes.
Two Salmonella vaccines currently exist, but neither is well suited for the communities most affected by the disease. Both offer only about 50 percent protection and face significant barriers to practical use in resource limited settings in Asia and Africa.
“These forms of the disease are really impactful for resource poor communities in Asia and Africa where the vaccines are either nonexistent or terrible,” said McSorley. “They are diseases of poverty.”
What Comes Next for Salmonella Vaccine Research
With the identification of non-circulating liver memory T cells as the critical driver of Salmonella immunity, the research team now has a clear target for vaccine design.
“Now that we know these forms of T cells exist and protect against Salmonella, the next goal is to try to develop synthetic ways to induce them to make a vaccine,” McSorley said.
The team is already exploring how to use vaccine components in mouse models to specifically stimulate these non-circulating cells. If successful, the approach could yield a Salmonella vaccine that is significantly more effective than anything currently available.
“If we can learn how to better induce them and if we can apply that to a new Salmonella vaccine, it should be more efficient at providing immunity than previous vaccines.”
This research was supported by the NIH’s National Institute of Allergy and Infectious Diseases and the National Health and Medical Research Council of Australia. Coauthors represented UC Davis’s School of Veterinary Medicine, the University of Melbourne, and the University of Connecticut.
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