Why will be you do this study?

Salmonella is a kind of bacteria that causes diarrhea and represents a public health problem in many countries. Children, especially infants, are most likely to get sick from it. This infection can be prevented by good hygiene practices and by vaccination. Information obtained from your participation in this study will inform on a vaccine that can provide protection against this infection and can be incorporated into the Expanded Program on Immunization could potentially control this lethal bacterial infection.

What questions are we trying to answer?

This study will evaluate stepwise a single dose of Full-strength and Half-strength Trivalent Salmonella Conjugate Vaccine (TSCV) administered to adults and then in progressively younger age groups down to 12 to 18 weeks of age, while comparing the safety and immunogenicity to controls who will receive Typbar-TCV™ or placebo. The trial will proceed from adults, to children, to toddlers, and then to infants.
 

Where is the study taking place?

This study will take place in selected public hospitals in Kenya, Mali and Mozambique

This study will aim to enroll healthy children and adults.
 

How many participants does it involve?

This trial will enroll 180 healthy participants per TSCV formulation group within this age range.
 

How will they be selected?

Participants in this study will be healthy individuals of both gender. Individuals with known hypersensitivity to any component of TSCV and previous vaccination with any licensed or experimental typhoid vaccine will be excluded. 

What does the study involve for those taking part?

Individuals taking part in this study will be carefully screened then randomly assigned to one of the groups to either receive the receive TSCV, Typbar-TCV, or placebo, then followed up. Blood samples will be collected from the study participants to measure how well the vaccines works, and measures the type of immune responses that the vaccine generates and their magnitude over time. 
 

What are the risks and benefits of taking part?

The participants in this study may experience some mild localized pain at the injection site, mild fatigue post-vaccination, vomiting, redness and swelling at the injection site, excessive crying, loss of appetite, irritability, headache, common cold, diarrhea and nausea and vomiting. These symptoms typically resolve in 48 hours. 

The study participants may benefit by taking part in this study since randomly allocated study participants will receive a dose of the vaccine and thus will benefit from protection against typhoid fever.
 

How will the study benefit society?

The findings from this study will provide science-based evidence for the need of a vaccine formulation that can provide protection against this lethal infection and can be incorporated into the Expanded Program on Immunization could potentially control this lethal bacterial infection.
 

When does the study start and finish?

This project is planned to start enrollment in March 2023 and to end recruitment in December 2025.

Invasive non-typhoidal Salmonella are an important cause of bacterial infections in sub-Saharan Africa and are associated with a high case fatality. Most cases are known to occur in children less than 5 years of age and are attributable to specific serovars. Detailed serotyping of iNTS isolates in Mali revealed that about 87% of all NTS invasive illnesses were caused by two Group B Salmonella serovars (S. Typhimurium and I:4,5,12:I) and two Group D serovars (S. Enteritidis and S. Dublin). This indicated that if an effective vaccine could be developed based on eliciting protection against Group B and D Salmonella serovars, it would be plausible to control this lethal pediatric infectious scourge by introducing a vaccine into the infant Expanded Program on Immunization (EPI) schedule. It was also noted that important risk factors for the development of serious iNTS infections included malaria infection accompanied by severe anemia, and immunocompromise due to untreated HIV infection. This implies that if one could administer a highly immunogenic vaccine against iNTS early in life, one could protect the infants, at a point when the risk of iNTS disease is greater. Therefore, a vaccine that can provide protection against these serovars and can be incorporated into the Expanded Program on Immunization could potentially control this lethal infection is urgently needed. 

This phase II trial will be an age-descending, randomized, placebo-controlled multicenter trial that will evaluate the safety and immunogenicity of a Trivalent Salmonella conjugate vaccine (TSCV). The trial will proceed from adults, to children, to toddlers, and then to infants. Individuals meeting the inclusion criteria will be randomly assigned to either receive TSCV, Typbar-TCV, or placebo. Venous blood will be collected for the measurement of serum-based immune response prior to vaccination (Day 1), 4 weeks (Day 29), 6 months (Day 181) after each study vaccination. Additional sample may be collected 1 year after study vaccination. Study participants who withdraw early or are lost to follow-up will have their immune response measures on available sera. In addition, memory B cells (B_M) specific for Vi, S. Typhimurium and S. Enteritidis LPS, as well as FliC and TT prior to vaccination (Day 1), 4 weeks (Day 29), and 6 months (Day 181) after each study vaccination will be measured. The duration of individual participation, including screening, ranges from 6 months to 18 months. The end-of-study is considered as the completion of the last visit for the last participant in the study.

The Kenyan site will enroll up to 180 healthy participants per TSCV formulation group within this age range (12 weeks to 35 years) The study will provide information on efficacy, immunogenicity and safety of the selected formulation when administered to pediatric and adult participants.