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EVALUATING A MULTI-VALENT AEROSOL BOOSTER TB VACCINE FOR ADOLESCENTS AND YOUNG ADULTS IN DIVERSE AFRICAN SETTINGS: T5 TBVAC

Project description

A new generation of vaccines to fight tuberculosis

Tuberculosis remains one of the world’s deadliest infectious diseases, highlighting the urgent need for more effective vaccines. The EU-funded T5-TBVAC project is developing the next generation of tuberculosis booster vaccines by evaluating the innovative ChAdOx1 T5 vaccine, which is designed to induce broader immune responses and improve protection against tuberculosis. Researchers will conduct clinical trials in the UK and sub-Saharan Africa, including the first aerosol delivery studies of a TB vaccine in the region and the transfer of a controlled human infection model to Uganda to evaluate vaccine performance and accelerate future vaccine development. Overall, the project aims to identify immune markers of protection, accelerate the development of future tuberculosis vaccines, and strengthen global partnerships for vaccine innovation.

Objective

In this proposal we will move beyond state-of-the-art in 3 ways. First, we will diversify the TB vaccine pipeline by developing the first multivalent recombinant viral vector TB vaccine candidate, ChAdOx1 T5, as a subunit booster vaccine for adolescents and young adults. We will compare immunogenicity between contrasting UK, West and East African settings. Second, ChAdOx1 T5 will be the first candidate TB vaccine delivered by aerosol in sub-Saharan Africa with bronchoscopic monitoring of lung immunity. Third, we will transfer an established and validated controlled human infection model (CHIM) to Uganda to compare ChAdOx1 T5 protective efficacy between rural and urban Uganda and the UK.
ChAdOx1 T5 expresses 5 mycobacterial antigens, each protective when delivered alone. Boosting prior BCG with ChAdOx1 T5 confers significant protection in mice and non-human primates. We will manufacture GMP ChAdOx1 T5 and conduct a UK first-in-human phase 1 clinical trial, followed by phase 2a trials in Senegal and Uganda, to determine the safety and immunogenicity of ChAdOx1 T5 when delivered either by aerosol or intramuscularly. We will use the skin BCG CHIM to evaluate the efficacy of ChAdOx1 T5 after either aerosol or intramuscular delivery in Uganda and the UK. Using a CHIM will significantly de-risk future, late-stage development of this and other candidate TB vaccines. A comprehensive analysis of immunological samples taken prior to BCG challenge will allow identification of immune correlates of protection which will support development of this and other candidate vaccines. Community engagement and involvement will guide our research processes and build population preparedness for new TB vaccine implementation. Capacity strengthening will be embedded in all that we do.
This proposal will develop the next generation TB subunit aerosol booster vaccine, de-risk its late-stage development and establish a strong South-South-North collaborative partnership for future TB vaccine R&D.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-JU-RIA - HORIZON JU Research and Innovation Actions

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Call for proposal

(opens in new window) HORIZON-JU-GH-EDCTP3-2025-01-two-stage

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 7 414 661,75
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom
Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 7 414 661,75

Participants (3)