Dr Elena Stylianou, University of Oxford, UK - VALIDATE Fellow
Defining the mechanism of BCG-priming and its impact on subunit vaccine boosting
Project Aims
Tuberculosis (TB) remains a significant global health challenge, claiming 1.6 million deaths annually. Mycobacterium tuberculosis (M.tb), the causative agent of TB, primarily targets the lungs, necessitating a vaccine capable of eliciting a robust lung immunity. However, the current TB vaccine, Bacillus Calmette-Guerin (BCG), gives some protection in children but fails to adequately protect adults, where most TB cases occur. This deficiency could stem from BCG’s inability to induce strong lung responses.
To improve BCG, I administered a viral vector vaccine, ChAdOx1.PPE15, expressing a protective mycobacterial antigen, PPE15, into the lungs. This strategy was shown to improve BCG in mice, likely due to improved lung responses. Understanding the immune responses behind ChAdOx1.PPE15 protection is critical for the design of better vaccine strategies.
In this project, I will examine the levels of PPE15-specific responses induced by two BCG administration routes, intravenous and intranasal, previously shown to result in stronger lung responses compared to the traditional intradermal route. In this way, I aim to identify mechanisms underlying protective lung immunity. Moreover, by utilising ChAdOx1.PPE15 to boost different routes of BCG vaccination, I will test whether these modifications result in improved protective outcomes.
I also plan to utilise the concept of ‘prime-pull’ vaccination, where a sequential systemic and intranasal vaccination with the same vaccine, was previously shown to enhance lung immune responses and efficacy. In these experiments, mice will receive BCG followed by ChAdOx1.PPE15 injected systemically. Animals will then receive ChAdOx1.PPE15 in the lungs. Immune responses and protection will be compared between the groups.
This project aims to inform the refinement of subunit vaccines by unravelling the impact of BCG vaccination on antigen-specific responses. By identifying ways to improve these responses and assessing their correlation with enhanced efficacy, I aim to optimise vaccination strategies aimed at boosting BCG immunity.
Find out more about Dr Elena Stylianou here.
