Typhoid conjugate vaccine booster dose study

Plain English summary of protocol

Background and study aims
Typhoid fever is a bacterial infection that can cause severe disease and even death. Typhoid is spread through contaminated food and water, due to poor hygiene and sanitation conditions. In Nepal, typhoid fever causes a lot of disease, mostly in children.
There is a vaccine called the typhoid conjugate vaccine that can help prevent typhoid fever. Many countries, like Nepal in 2022, have started giving this vaccine to children as part of the routine childhood immunisation programme. New information from a study in Bangladesh shows that the vaccine might not work as well after three years, especially for children who had the vaccine when they were very young (under 2 years old). This is a problem because children usually get typhoid fever when they start school (around 5-6 years old). This means they might not be protected even if they had the vaccine as infants.
This study will test whether giving children a booster (an extra dose) of the vaccine before they start school will help keep them protected from typhoid fever. The study will try two different brands of the vaccine (called Typbar or Typhibev) to see which works best. This way, if the booster works well, governments will have more choices to help protect children from typhoid fever.

Who can participate?
Children who received the Vi-TT vaccine at 9 months to 2.5 years of age as part of the TyVAC study (OxTREC 15-17; NHRC 170-2017)

What does the study involve?
There are three parts involved in the study for participants:
1. Booster vaccination: participants will receive a second dose of a typhoid conjugate vaccine. This will be one of two brands of the vaccine: either the one used in the previous TyVAC study (Typbar) or the one used in the Nepal government schedule (Typhibev). These vaccines are both licensed for use in Nepal and have a good safety record.
2. Scheduled blood draws and follow-up visits: to monitor how well the vaccine is working and to check participants’ overall health, participants will undergo a few blood tests and follow-up assessments at specific times throughout the study. On the day of vaccination, a blood sample will be taken before administering the vaccine. Follow-up visits will occur at 28 days, 6 months, and 18 months post-vaccination. During these visits, a research doctor will carry out a physical examination, collect blood samples to evaluate the immune response to the vaccine, and track and document any adverse events or illnesses. Additionally, participants will be contacted periodically via phone or home visits to ensure their well-being and address any concerns.
3. Fever clinic attendance: in addition to the above, if a participant has a fever during the study period, they should attend Patan Hospital, where there will be study clinics. At the clinic, participants will be assessed, and if they have had a fever for over 48 hours, a blood sample to look for typhoid infection will be taken.

What are the possible benefits and risks of participating?
Benefits: The booster vaccine is designed to increase and prolong protection against typhoid fever compared to the regular vaccine. It will provide participants with increased and sustained protection and contribute to improving overall public health by supporting better vaccination strategies and policies.
Participants will also receive health check-ups by a doctor at the scheduled follow up visits (four visits total). If a participant develops a fever during the 18 months of the trial, they will be able to access routine medical care (including investigations) and treatment through the study hospital, and all costs will be covered by the study. Participants will also receive 500 NRS to cover travel costs for each scheduled study visit (four in total).
Risks: When having blood samples taken, participants may develop a small bruise afterwards, which should fade in a few days. Apart from the minimal risks associated with routine childhood vaccinations, such as mild pain and acute fever, there are no additional risks to participating in the study

Where is the study run from?
Patan Academy of Health Science, Kathmandu (Nepal)

When is the study starting and how long is it expected to run for?
September 2024 to November 2026

Who is funding the study?
The Wellcome Trust (UK)

Who is the main contact?
Prof. Andrew Pollard, info@ovg.ox.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• Nepal

Study participating centre

Sponsor information

University of Oxford
University/education

Wellington Square
Oxford
OX1 2JD
England
United Kingdom

Phone	+44 (0)1865 (2)82106
Email	oxtrec@admin.ox.ac.uk
Website	https://ror.org/052gg0110
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Research organisation

Results and Publications

Editorial Notes

09/06/2025: The primary outcome measure was changed.
27/05/2025: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/05/2025 to 01/12/2025.
2. The recruitment end date was changed from 30/06/2025 to 02/01/2026.
07/04/2025: Study's existence confirmed by the Oxford Tropical Research Ethics Committee (OxTREC).