Phase 1 Trial Finds Typhoid and Salmonella Vaccine Safe and Effective

A successful Phase 1 clinical trial has been completed for a new vaccine aimed at protecting against typhoid fever and invasive non-typhoidal Salmonella, two major causes of illness and child mortality in sub-Saharan Africa. The trial was conducted by the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine (1^✔ ✔Trusted Source
A combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine in healthy adults: a randomized, placebo-controlled phase 1 trial

Go to source). The findings, now published in Nature Medicine, detail the development of the Trivalent Salmonella Conjugate Vaccine. This investigational vaccine uses sugar molecules taken from the outer layer of Salmonella typhi, the bacteria responsible for typhoid and two other invasive Salmonella enterica types not linked to typhoid. These sugars are bound to special proteins that help the immune system detect and respond more effectively to the bacterial threats.

Strong Immune Response Observed in Adult Volunteers

In the randomized, placebo-controlled Phase 1 trial, 22 healthy adults in the United States received either a low dose of 6.25 micrograms or a high dose of 12.5 micrograms of the vaccine, while some received a placebo. The vaccine was found to be safe and well-tolerated, with only mild and short-lived pain at the injection site.

Notably, every person who received the vaccine developed a strong immune response to all three polysaccharide components included in the vaccine, whereas none of the placebo recipients exhibited such a response.

Vaccine Offers Hope in High-Risk Areas for Salmonella Infections

“This is an extremely promising result,” said Dr. Wilbur Chen, lead investigator and Professor of Medicine at the University of Maryland School of Medicine. He emphasized that the vaccine could protect children in areas where both types of Salmonella infections are prevalent and deadly.

In addition to its potential in Africa, the vaccine could also benefit Americans, as Salmonella is a leading cause of foodborne illness in the United States. According to the Centers for Disease Control and Prevention, there are 1.35 million cases and over 26,000 hospitalizations due to Salmonella infections annually in the United States often caused by bacteria in undercooked chicken, eggs, and contaminated produce. The specific Salmonella serotypes targeted by this vaccine are among the most common in those U.S. cases.

Stronger Immune Responses Expected in High-Risk Children

Some volunteers already had existing antibodies, likely due to previous exposure through foodborne illness. This pre-existing immunity may have boosted their immune response and could indicate long-lasting protection. Researchers remain hopeful that similar or stronger immune responses will be observed in young children in high-risk regions.

The vaccine was effective even at lower doses and stimulated not only antibody production but also activated a white blood cell-based immune defense. This dual immune activation, particularly the response involving white blood cells, had not previously been seen with one of the vaccine’s protein components and suggests the potential for both intestinal and systemic protection against Salmonella.

Next Steps Focused on Young Children and Broader Efficacy

“These findings set the stage for the next phases of development,” noted Dr. Myron Levine, co-author and professor emeritus at the University of Maryland School of Medicine. The next goal is to conduct broader functional immune response testing and assess the vaccine’s efficacy in infants and young children, who are most vulnerable to these infections.

The vaccine was co-developed with Bharat Biotech International Limited and builds upon their existing World Health Organization–prequalified platform for typhoid vaccines, Typbar TCV.

Urgent Need for Dual-Action Vaccine in Africa

“In 2017 alone, sub-Saharan Africa recorded more than 420,000 cases of Salmonella infections and 66,000 deaths, primarily in children,” said Dr. Mark T. Gladwin, Dean of the University of Maryland School of Medicine.

Typhoid fever added another 650,000 cases and nearly 9,000 deaths. A single vaccine capable of combating both diseases could transform pediatric health outcomes in such high-burden regions.

Reference:

1. A combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine in healthy adults: a randomized, placebo-controlled phase 1 trial - (https://www.nature.com/articles/s41591-025-04003-z)

Source-Eurekalert