Researchers at the University of Maryland School of Medicine's Center for Vaccine Development and Global Health (CVD) have achieved a significant milestone in combating two major bacterial threats to children in sub-Saharan Africa. Their Phase 1 clinical trial of a novel trivalent Salmonella conjugate vaccine (TSCV) demonstrated remarkable safety and immunogenicity results, with 100% of participants developing strong immune responses to all three targeted bacterial components.
The investigational vaccine addresses a critical global health challenge, targeting both typhoid fever and invasive non-typhoidal Salmonella (iNTS) infections. In 2017, sub-Saharan Africa experienced over 420,000 cases of Salmonella disease resulting in 66,000 deaths, primarily among children. Typhoid fever contributed an additional 650,000 cases and nearly 9,000 deaths in the region.
Vaccine Design and Mechanism
The TSCV combines sugar molecules (polysaccharides) from the outer coating of Salmonella typhi bacteria with components from the two most common types of invasive Salmonella infections caused by Salmonella enterica serovars Typhimurium and Enteritidis. These polysaccharides are conjugated to specialized carrier proteins, including flagellin proteins that enhance the body's immune response.
The vaccine builds upon Bharat Biotech International Limited's WHO-prequalified Typbar TCV™ platform, incorporating the Vi capsular polysaccharide with tetanus toxoid and core-plus-O-polysaccharides from the two prevalent iNTS serovars. This combination targets Salmonella enterica serovar Typhi and the serovars that account for roughly 90% of iNTS infections in young children.
Phase 1 Trial Results
The randomized, placebo-controlled trial enrolled 22 healthy adults aged 18 to 45 in the United States. Participants received either a low dose (6.25 μg), high dose (12.5 μg), or placebo injection. The primary safety endpoints focused on serious and non-serious adverse events, while the primary immunogenicity endpoint measured serum immunoglobulin G (IgG) responses against the three vaccine polysaccharides and two flagellin carrier proteins.
"These results are highly encouraging," said study lead investigator Wilbur Chen, MD, MS, Professor of Medicine at UM School of Medicine and Chief of the Adult Clinical Studies section within CVD. "They show that TSCV has the potential to protect children in regions where both typhoid and salmonella are endemic and deadly."
The vaccine demonstrated exceptional safety, with no serious adverse events reported among TSCV recipients. All solicited reactions were mild or moderate, with only mild, short-lived injection site pain documented. Immunogenicity analysis revealed strong immune responses to all three polysaccharide components in all TSCV recipients regardless of dose at 28 days post-vaccination. The flagellin components elicited responses in 7 of 8 volunteers receiving the low dose and all participants receiving the high dose.
Sustained Immune Response
A particularly encouraging finding was the persistence of antibodies at levels fourfold higher than baseline among TSCV recipients more than a year after vaccination. This durability was observed despite delays in specimen collection due to the COVID-19 pandemic. The vaccine triggered both strong antibody responses and activated specific immune defenses involving white blood cells that help clear infections.
Some study participants showed pre-existing antibody responses, suggesting prior exposure to the bacteria through foodborne illness. This priming may have contributed to the stronger and longer-lasting immunity observed in the adult volunteers, though researchers remain optimistic about the vaccine's effectiveness in infants and young children in endemic regions.
Broader Implications
Beyond its potential impact in sub-Saharan Africa, the vaccine could benefit populations in high-income countries where Salmonella remains a significant cause of foodborne illness. In the United States, Salmonella bacteria from raw or undercooked chicken and eggs and contaminated produce cause 1.35 million infections annually and more than 26,000 hospitalizations, according to the Centers for Disease Control and Prevention. The serotypes targeted by TSCV are among the most common in US infections.
"A single vaccine that protects against both could be a game-changer for global pediatric health," said Mark T. Gladwin, MD, Dean of the UM School of Medicine.
Future Development Plans
Study co-author Myron Levine, MD, DTPH, professor emeritus at UM School of Medicine and CVD founding director, outlined the next steps: "These findings provide a strong foundation for future studies. We plan to explore broader functional assays to identify correlates of protection and evaluate TSCV's performance in young children-the population most vulnerable to these diseases."
The research team plans to conduct trials assessing safety and immunogenicity in young infants and toddlers in sub-Saharan Africa, followed by a large Phase 3 field trial to establish protective efficacy. Investigators also intend to evaluate whether TSCV can be co-administered with routine childhood vaccines, which would be crucial for implementation in pediatric immunization programs.
The findings, published in Nature Medicine, represent a collaborative effort between the University of Maryland School of Medicine and Bharat Biotech International Limited, demonstrating the potential of innovative vaccine platforms to address multiple related pathogens with a single intervention.
