New Phase 1 results offer hope for a dual-protection vaccine
A novel trivalent vaccine designed to guard against both typhoid fever and invasive non-typhoidal Salmonella (iNTS) infections has demonstrated encouraging safety and immune responses in a Phase 1 human trial. The study, led by researchers from the University of Maryland (UM) School of Medicine in collaboration with Bharat Biotech, was published in Nature Medicine and signals a potential breakthrough in protecting children in regions where typhoid and iNTS are deadly threats.
What makes this vaccine unique
The vaccine—referred to as the trivalent Salmonella conjugate vaccine (TSVC)—is designed to target Salmonella enterica serovar Typhi (typhoid) and the two serovars Typhimurium and Enteritidis, which account for most iNTS infections in young children. The researchers combined Bharat Biotech’s licensed Typbar TCV Vi polysaccharide with tetanus toxoid and core-plus-O-polysaccharides from the two iNTS serovars. These components are then conjugated to two flagellin carrier proteins to boost the immune response. By including both typhoid and iNTS targets, the vaccine aims to offer broad protection against the major invasive Salmonella pathogens that affect children in sub-Saharan Africa and other high-burden regions.
How the vaccine is expected to work
TSVC represents a strategic blend of well-established elements (the Typbar TCV components) with novel conjugates specific to iNTS. The goal is to generate robust antibody responses against three polysaccharide components and two flagellin proteins, increasing the likelihood of protection against both typhoid fever and severe invasive Salmonella infections. If successful in later-stage trials, the vaccine could streamline immunization strategies by addressing multiple pathogens with a single dose schedule.
Phase 1 trial results: safety and immunogenicity
In the Phase 1 trial, 22 healthy adults in the United States aged 18 to 45 were given either a low dose (6.25 µg), a high dose (12.5 µg) of TSVC, or a placebo. Safety monitoring showed no serious adverse events among those receiving TSVC. Reactions were generally mild to moderate, aligned with what is expected from conjugate vaccines. In terms of immune response, all three polysaccharide targets elicited strong serum IgG responses across vaccine recipients, with the journey to robust immunity beginning as early as 28 days after vaccination.
Regarding the two flagellin components, responses were observed in most recipients: 7 of 8 in the low-dose group and all individuals in the high-dose group demonstrated immune activity against the flagellin proteins. Notably, antibody levels remained elevated—roughly four times higher than baseline—for more than a year in those vaccinated, even with COVID-19-era delays in sample collection affecting long-term follow-up.
Implications for future research and public health
Lead investigator Dr. Wilbur Chen highlighted the study’s significance, noting that a single vaccine offering protection against both typhoid and iNTS could be a game-changer for pediatric health in regions where these infections are endemic. The Phase 1 results are preliminary, and the small sample size means that further research is needed to confirm safety, optimal dosing, and real-world effectiveness. However, the positive safety profile and strong immunogenicity provide a solid foundation for advancing to Phase 2 and 3 trials that would evaluate efficacy in children and broader populations.
In regions like sub-Saharan Africa, where typhoid fever and invasive iNTS remain leading causes of childhood illness and death, a successful multivalent vaccine could transform disease prevention. If subsequent trials validate the findings, health authorities and vaccination programs might gain a new tool to reduce disease burden, streamline immunization efforts, and improve outcomes for some of the world’s most vulnerable children.
What comes next
The researchers plan to pursue larger, more diverse populations in future trial phases to assess safety and effectiveness across age groups, including children. Regulatory reviews will guide the pace of development, and the global health community will be watching closely for results that could influence vaccine policy and implementation in high-need settings.
