Related Experiment Video
Updated: Jan 2, 2026
Author Spotlight: Optimizing CFU Determination for Efficient Assessment of TB Vaccine Efficacy and Antigen Presentation Analysis
Published on: July 28, 2023
Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal
Mila Shakya1, Rachel Colin-Jones1, Katherine Theiss-Nyland1
1From the Oxford University Clinical Research Unit (M.S., S.D., A.K., B. Basnyat), Patan Academy of Health Sciences, Patan Hospital (D.P., M.G., S.S.), the Nepal Family Development Foundation (A.A.), and Wasa Pasa Polyclinics Private, Lalitpur (B. Bajracharya) - all in Kathmandu; the Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research Oxford Biomedical Research Centre, Oxford (R.C.-J., K.T.-N., M.V., N.S., X.L., S.T., O.M., Y.G.F., J.C., J.H., S.K., A.J.P.), and the Department of Medicine, University of Cambridge, Cambridge (S.B.) - all in the United Kingdom; the Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (S.B.); and the University of Maryland School of Medicine, Baltimore (K.M.N.).
Insights
A typhoid conjugate vaccine (TCV) significantly reduced typhoid fever in children in Nepal. This vaccine is immunogenic and effective, offering a new tool against this common childhood illness.
Area of Science:
- * Infectious Diseases
- * Vaccinology
- * Global Health
Background:
- * Typhoid fever, caused by *Salmonella* Typhi, is a significant health concern for children in low- and middle-income countries.
- * A recently WHO-prequalified typhoid conjugate vaccine (TCV) demonstrated efficacy in challenge models, but real-world data from endemic areas were needed.
Purpose of the Study:
- * To evaluate the efficacy and safety of a typhoid conjugate vaccine (TCV) in a phase 3 randomized controlled trial.
- * To assess the immunogenicity of TCV compared to a control vaccine in children.
Main Methods:
- * A phase 3, randomized, double-blind, controlled trial was conducted in Nepal involving children aged 9 months to 16 years.
- * Participants were assigned 1:1 to receive either TCV or a meningococcal serogroup A conjugate vaccine (MenA) as a control.
- * The primary outcome was culture-confirmed typhoid fever; immunogenicity was assessed in a subgroup.
Main Results:
- * Typhoid fever incidence was significantly lower in the TCV group (79 cases/100,000 person-years) versus the MenA group (428 cases/100,000 person-years), yielding 81.6% vaccine efficacy.
- * Seroconversion rates were high (99%) in the TCV group compared to the MenA group (2%).
- * Adverse events were similar between groups, with no significant safety concerns identified for TCV.
Conclusions:
- * A single dose of TCV is highly immunogenic and effective in preventing *Salmonella* Typhi bacteremia in children.
- * TCV represents a promising intervention for controlling typhoid fever in endemic regions.
Background:
Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking.
Methods:
In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing.
Results:
A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P<0.001). A total of 132 serious adverse events (61 in the TCV group and 71 in the MenA vaccine group) occurred in the first 6 months, and 1 event (pyrexia) was identified as being vaccine-related; the participant remained unaware of the trial-group assignment. Similar rates of adverse events were noted in the two trial groups; fever developed in 5.0% of participants in the TCV group and 5.4% in the MenA vaccine group in the first week after vaccination. In the immunogenicity subgroup, seroconversion (a Vi IgG level that at least quadrupled 28 days after vaccination) was 99% in the TCV group (677 of 683 participants) and 2% in the MenA vaccine group (8 of 380 participants).
Conclusions:
A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age. (Funded by the Bill and Melinda Gates Foundation; Current Controlled Trials number, ISRCTN43385161.).
Related Concept Videos
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:19Phase II Reactions: Miscellaneous Conjugation Reactions
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
01:11Clinical Trials: Overview