Researchers close out successful clinical trial of novel trivalent vaccine for Salmonella, typhoid

A Phase 1 clinical trial led by researchers at the University of Maryland School of Medicine has demonstrated that a novel trivalent Salmonella conjugate vaccine (TSCV) is safe, well tolerated and capable of generating strong immune responses against typhoid and invasive non-typhoidal Salmonella — two major causes of childhood illness and death in sub-Saharan Africa

Researchers at the Center for Vaccine Development and Global Health (CVD) at the University of Maryland School of Medicine have completed a successful Phase 1 clinical trial of a novel vaccine intended to confer protection against both typhoid fever and invasive non-typhoidal Salmonella – two leading causes of illness and death among children in sub-Saharan Africa.

The investigational trivalent Salmonella conjugate vaccine (TSCV) comprises sugar molecules derived from the outer coating of Salmonella typhi – the causative agent of typhoid – and from the two most common non-typhoidal Salmonella enterica serotypes associated with invasive disease. These polysaccharides are conjugated to specialised proteins intended to elicit a stronger immune recognition and response.

In the randomised, placebo-controlled Phase 1 trial, 22 healthy adult volunteers in the United States received either a low dose (6.25 µg) or high dose (12.5 µg) of TSCV, or a placebo injection. The vaccine was deemed safe and well tolerated, with only mild, transient injection-site pain reported. Crucially, all vaccine recipients mounted robust immune responses to each of the three polysaccharide components, whereas none of the placebo recipients did.

“These results are highly encouraging,” said the study lead investigator, Dr. Wilbur Chen, MD, MS, professor of medicine at the University of Maryland School of Medicine and Chief of the Adult Clinical Studies section at CVD.

“They show that TSCV has the potential to protect children in regions where both typhoid and Salmonella are endemic and lethal,” he added.

The vaccine could also offer widespread protection against Salmonella infections, which constitute a major cause of foodborne disease. For example, each year in the United States, bacteria from raw or undercooked poultry, eggs and contaminated produce cause 1.35 million Salmonella infections and more than 26,000 hospitalisations, according to the US Centers for Disease Control and Prevention (CDC).

Some trial participants exhibited pre-existing antibody responses, implying past exposure to Salmonella via foodborne illness. Such immunological priming could have bolstered the strength and durability of vaccine-induced immunity in these adult volunteers. Investigators remain optimistic that TSCV will perform effectively in infants and young children in endemic settings.

The vaccine elicited a strong and balanced immune reaction, including sustained antibody production even at the lower dose. It also stimulated a particular cellular immune response involving white blood cells that assist in infection clearance — a response not previously recorded for one of the vaccine’s protein components. These observations suggest that TSCV may confer both mucosal (gut-level) and systemic protection against Salmonella.

“These findings provide a strong foundation for future studies,” said study co-author Myron Levine, MD, DTPH, Professor Emeritus at the University of Maryland School of Medicine and founding director of CVD. “We plan to pursue broader functional assays to identify correlates of protection and to assess TSCV’s performance in young children — the group most susceptible to these diseases.”

The vaccine was developed in collaboration with Bharat Biotech International Limited (BBIL), building on their WHO-prequalified Typbar TCV™ platform.

“In 2017, sub-Saharan Africa recorded more than 420,000 cases of Salmonella disease and 66,000 deaths, mostly among children,” said Dr. Mark T. Gladwin, MD, Dean of the University of Maryland School of Medicine.

“Typhoid fever caused an additional 650,000 cases and nearly 9,000 deaths in the region. A single vaccine that confers protection against both could transform global paediatric health,” he concluded.

For further reading please visit: 10.1038/s41591-025-04003-z