A novel vaccine designed to combat both typhoid fever and invasive non-typhoidal Salmonella (iNTS) infections has shown promising results in an initial human trial, raising hopes for better protection against deadly infections that affect children worldwide. The vaccine, tested in healthy adults, triggered strong immune responses while proving safe and well-tolerated, researchers reported.Led by investigators from the University of Maryland (UM) School of Medicine, the phase 1 trial assessed a trivalent Salmonella conjugate vaccine (TSVC) aimed at preventing typhoid fever and severe bloodstream infections caused by non-typhoidal Salmonella. The results were published in Nature Medicine.UM School of Medicine Dean Mark Gladwin, MD, said in a university press release: “A single vaccine that protects against both could be a game-changer for global pediatric health.” Typhoid fever and iNTS are among the leading causes of illness and death in children in Africa, making such a vaccine highly significant.
How the vaccine works
TSVC was developed jointly by UM’s Center for Vaccine Development and Global Health (CVD) and Bharat Biotech International Limited. It targets Salmonella enterica serovar Typhi, responsible for typhoid fever, as well as serovars Typhimurium and Enteritidis, which account for about 90% of iNTS infections in young children.The vaccine combines the Vi capsular polysaccharide from Bharat Biotech’s licensed typhoid conjugate vaccine (Typbar TCV) with tetanus toxoid and core-plus-O-polysaccharides from the two most prevalent iNTS serovars. These are conjugated to two flagellin carrier proteins to enhance the immune response.The authors of the Nature Medicine study explained: “Combination of the two iNTS conjugates with licensed Typbar TCV (Vi-TT) achieves a trivalent conjugate that is intended, collectively, to elicit protection against all the major invasive Salmonella pathogens that threaten young children in SSA.”
Results from phase 1 trial
To evaluate safety and immune response, 22 healthy US adults aged 18 to 45 were enrolled. Participants received either a low dose (6.25 µg), a high dose (12.5 µg) of the vaccine, or a placebo. The trial monitored both serious and non-serious adverse events and measured the serum immunoglobulin G (IgG) response against the three vaccine polysaccharides and the two flagellin proteins.No serious adverse events occurred among TSCV recipients. All reported reactions were mild or moderate. Immune responses were robust for all three polysaccharide components in every vaccine recipient 28 days after vaccination. The two flagellin components elicited a response in 7 of 8 low-dose recipients and all high-dose recipients. Placebo recipients showed no response.Notably, antibodies remained at levels four times higher than baseline in vaccine recipients more than a year later, despite delays in blood sample collection caused by the COVID-19 pandemic.
Previous exposure may enhance immunity
Lead investigator Wilbur Chen, MD, chief of the adult clinical studies section at CVD, said in a UM press release: “These results are highly encouraging. They show that TSCV has the potential to protect children in regions where both typhoid and salmonella are endemic and deadly.”The investigators also noted that prior exposure to Salmonella among participants might have strengthened the immune response. While the trial was small, the findings support further research to confirm both safety and effectiveness.