A promising new vaccine developed by researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) has shown strong potential to protect against both typhoid fever and invasive non-typhoidal Salmonella (iNTS), two serious infections that cause thousands of deaths every year, particularly among children in sub-Saharan Africa. The Phase 1 clinical trial findings, published in Nature Medicine, evaluated the Trivalent Salmonella Conjugate Vaccine (TSCV).
The investigational TSCV is formulated using sugar molecules derived from the outer surface of Salmonella typhi, the bacterium responsible for typhoid fever, as well as from two major Salmonella enterica strains that cause invasive non-typhoidal Salmonella infections. These sugars are chemically linked to carrier proteins, which enhance the body’s ability to recognize the bacteria and mount a stronger, more effective immune response.
In a randomized placebo-controlled trial of 22 healthy U.S. adults, participants received either a low dose, high dose, or placebo. Results showed excellent safety, minimal side effects, and robust immune responses in all vaccinated participants, with no comparable response in the placebo group. According to lead investigator Dr. Wilbur Chen, these early findings are highly encouraging and suggest that TSCV could offer lifesaving protection for children in regions where these infections are common. Beyond global health benefits, the vaccine may also have public health implications in the United States, where Salmonella remains a leading cause of foodborne illness, responsible for approximately 1.35 million infections and over 26,000 hospitalizations every year.
Researchers also observed that some participants had pre-existing antibodies, likely from prior foodborne exposure, indicating that the vaccine may enhance existing immunity and provide durable protection. Moreover, TSCV triggered a broad and long-lasting immune response, including strong antibody production, activation of infection-fighting white blood cells, and a newly identified immune response to one of its protein components.
Similarly, An and colleagues demonstrate that iNTS O-specific polysaccharide diphtheria toxoid conjugates in a bivalent formulation with alum induce strong immune responses against S. Typhimurium and S. Enteritidis, and that a trivalent formulation combining this bivalent iNTS vaccine with a typhoid conjugate vaccine maintains robust immunogenicity. This approach offers potential broad protection against both iNTS and typhoid fever in high-burden areas.
These findings highlight TSCV’s potential as a powerful dual-action vaccine capable of providing both gut-level and systemic protection against Salmonella infections worldwide.
References
- Chen WH, Barnes RS, Sikorski MJ, Datar R, Sukhavasi R, Liang Y, Rapaka RR, Pasetti MF, Sztein MB, Wahid R, Tennant SM, Simon R, Baliban SM, Galen JE, Lees A, Bernshtein B, Alter G, Ella R, Mohan K, Naidu MG, Rao DY, Ella KM, Levine MM. A phase 1 randomized, placebo-controlled trial of a combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine. medRxiv [Preprint]. 2025 Sep 18:2025.09.15.25335795.
- An SJ, Yang JS, Chae MH, Woo JS, Kang YE, Ganapathy R, Pansuriya RK, Choi JA, Yoon YK, Lee E, Lee SB, Pandey G, Lee JW, Lee JS, Bae SH, Kweon SW, Kim SJ, Seon SH, Kim JH, Song M. Development of invasive non-typhoidal Salmonella conjugate vaccines and their evaluation in a trivalent formulation with typhoid conjugate vaccine. Vaccine. 2025 Apr 11;52:126913.