Overview: A New Hope Against Typhoid and iNTS
A novel trivalent vaccine designed to protect against both typhoid fever and invasive non-typhoidal Salmonella (iNTS) infections has shown promising safety and robust immune responses in an initial human trial. The Phase 1 study, led by researchers from the University of Maryland (UM) School of Medicine in collaboration with Bharat Biotech, marks a potential turning point in the fight against deadly childhood infections that disproportionately affect sub-Saharan Africa and other vulnerable regions.
The vaccine, referred to as TSVC, targets Salmonella enterica serovar Typhi—the causative agent of typhoid fever—and the two most common iNTS serovars, Typhimurium and Enteritidis. By combining components from established typhoid and iNTS vaccines into a single formulation, the researchers aim to offer broad protection against the major invasive Salmonella pathogens that threaten young children in low-resource settings.
How the TSVC Vaccine Works
The TSVC design builds on two proven strategies. First, it uses the Vi capsular polysaccharide from Bharat Biotech’s Typbar TCV typhoid vaccine, conjugated to tetanus toxoid to enhance immune recognition. Second, it incorporates core-plus-O-polysaccharides from the two leading iNTS serovars, conjugated to flagellin carrier proteins to boost the body’s antibody response. The result is a trivalent formulation that the researchers hope will elicit protective immunity against the major invasive Salmonella threats affecting children in Africa and other regions with high disease burden.
According to the Nature Medicine report detailing the study, the combination of the two iNTS components with the licensed Typbar TCV creates a single vaccine designed to address all the principal invasive Salmonella pathogens in affected populations. This approach could simplify immunization schedules and improve uptake where multiple vaccines are currently required.
Phase 1 Trial: Design and Early Safety Signals
The Phase 1 trial enrolled 22 healthy adults aged 18 to 45 in the United States to evaluate safety and immune responses, rather than clinical efficacy. Participants were randomized to receive either a low-dose (6.25 µg) or high-dose (12.5 µg) TSVC or a placebo. The study tracked adverse events and measured serum immunoglobulin G (IgG) responses against the three polysaccharide components and the two flagellin proteins over 28 days, with additional follow-up to assess durability of the response.
Safety and Reactogenicity
Overall, TSVC was well tolerated. No serious adverse events were reported among vaccine recipients. Most adverse events were mild or moderate and consistent with typical responses to other conjugate vaccines, such as soreness at the injection site or transient fatigue. This safety profile is encouraging for a multicomponent vaccine, which often raises questions about tolerability in diverse populations.
Immunogenicity and Early Signals of Durability
Importantly, immune responses were robust for all three polysaccharide components in every recipient by day 28. The two iNTS-related flagellin components elicited strong responses in most participants, with nearly all high-dose recipients showing measurable antibodies. Notably, antibodies remained fourfold above baseline for more than a year in many vaccinees, suggesting durable immunity despite pandemic-related delays in blood sample collection.
Implications for Global Health
Lead investigator Wilbur Chen, MD, emphasized the potential impact of a dual-action vaccine, particularly for children in regions where typhoid and iNTS are endemic and deadly. The trial’s small size means that results must be confirmed in larger, more diverse populations, including children, to establish true safety and effectiveness. Still, the Phase 1 findings strengthen the rationale for continued development and eventual field trials in affected regions.
Next Steps
Researchers plan to advance TSVC into subsequent clinical stages to evaluate safety in broader age groups and to explore actual protection against infection in real-world settings. If future trials replicate the encouraging safety and immunogenicity signals seen in this Phase 1 study, the vaccine could become a critical tool in reducing childhood morbidity and mortality from typhoid and invasive Salmonella infections.
In a university press release, UM School of Medicine Dean Mark Gladwin, MD, described the work as potentially transformative: “A single vaccine that protects against both could be a game-changer for global pediatric health.”
