promising Phase 1 results for a novel Typhoid and iNTS vaccine
A new trivalent vaccine designed to protect against typhoid fever and invasive non-typhoidal Salmonella (iNTS) infections has demonstrated encouraging safety and immune responses in a Phase 1 human trial. Developed through a collaboration between the University of Maryland (UM) School of Medicine and Bharat Biotech, the vaccine aims to shield children in regions where typhoid and iNTS remain deadly threats. The study, published in Nature Medicine, marks an important step toward a single vaccine that could reduce illness and death from multiple Salmonella-related diseases.
How the vaccine works
The vaccine, named a trivalent Salmonella conjugate vaccine (TSVC), brings together components targeting three major Salmonella pathogens: Salmonella Typhi (typhoid fever) and the two most common iNTS serovars, Typhimurium and Enteritidis. The strategy combines the Vi capsular polysaccharide from a licensed Typbar TCV typhoid vaccine with a conjugation approach designed to boost immunity. Specifically, the Vi polysaccharide and iNTS components are linked to carrier proteins, including tetanus toxoid and core-plus-O-polysaccharides, and two flagellin proteins to enhance the immune response. This design aims to elicit protection against the most prevalent invasive Salmonella threats affecting young children in sub-Saharan Africa and other regions with high disease burden.
The Phase 1 trial: safety and immune response
The early study enrolled 22 healthy adults aged 18 to 45 in the United States. Participants were randomized to receive a low dose (6.25 µg), a high dose (12.5 µg) of TSVC, or a placebo. Researchers tracked adverse events and measured serum immunoglobulin G (IgG) responses against the three polysaccharide targets and the two flagellin proteins. The trial reported no serious adverse events among vaccine recipients. Reactions were generally mild or moderate, and the immune responses were robust for all three polysaccharide components across recipients by day 28.
Importantly, antibodies remained four times higher than baseline in vaccine recipients for more than a year, even with pandemic-related sampling delays. The two flagellin components also produced strong responses: seven of eight low-dose recipients and all high-dose recipients showed activations, while placebo recipients showed no such response. These findings suggest the TSVC can provoke a multifaceted immune response against the key Salmonella strains responsible for typhoid and severe iNTS infections.
What the results mean for global health
Lead investigator Wilbur Chen, MD, highlighted the potential impact of a single vaccine that targets both typhoid and iNTS. The combination approach could be especially transformative for regions where both diseases are endemic and contribute to childhood morbidity and mortality. While the Phase 1 trial was small and conducted in healthy adults, the data support advancing to further studies to confirm safety and effectiveness in broader populations, including children in high-burden areas.
Senior researchers noted that prior exposure to Salmonella among participants may have enhanced observed immune responses, a factor that warrants consideration in subsequent trials across diverse populations. The Nature Medicine report underscores that these early signals justify continued development and larger, more diverse trials to establish real-world protection against the major invasive Salmonella pathogens that threaten young children in Africa and elsewhere.
Next steps and expectations
Researchers are planning further clinical evaluations to assess the vaccine’s safety profile in broader age groups and to determine optimal dosing strategies. If subsequent trials confirm safety and demonstrate protective efficacy, TSVC could advance to Phase 2/3 trials focused on pediatric populations, where the burden of typhoid and iNTS is most acute.
Conclusion
In sum, the TSVC represents a pioneering effort to combine protection against typhoid fever and invasive non-typhoidal Salmonella with a single immunization strategy. The Phase 1 results—strong safety signals, robust immune responses to all components, and sustained antibody levels—offer cautious optimism for a vaccine that could significantly reduce childhood illness and death caused by Salmonella in high-burden regions. As researchers prepare for larger trials, the global health community watches for whether this promising approach can translate into durable, real-world protection.
