Alvacc: A human in vitro alveolus model to study aerogenic TB vaccine binding and translocation
Led by Dr Diane Lee (University of Surrey, UK), with Prof Mark Chambers (University of Surrey, UK) and Prof Rajko Reljic (SGUL, UK)
Delivering tuberculosis (TB) vaccines directly to the lung by aerosol can result in efficient and better protection by directly targeting immune cells resident in the lung, as shown for BCG vaccine in non-human primates. However, optimising these processes is not trivial. Recent work has shown that protection conferred by BCG can be enhanced by subsequently administering another vaccine to the lung consisting of a harmless bacterial spore coated with proteins found in TB, called "Spore-FP1". The efficacy of Spore-FP1 stems from inclusion of the TB protein, HBHA. As the lung has evolved to normally exclude particles like Spore-FP1, HBHA is believed to improve attachment of the vaccine to the cells lining the alveoli of the lung followed by efficient transport of the vaccine across the alveolar barrier. In turn, this gives Spore-FP1 access to immune cells underlying the alveoli. However, direct experimental evidence for this is lacking. If we could show this was the case, better understanding these processes would allow us to design vaccines for delivery to the lung that are both safe and highly efficient at generating an immune reponse locally in the lung itself. However, these transient processes are difficult to study in animal models. We address this challenge in this project by studying how Spore-FP1 and BCG vaccines interact with and cross a human laboratory tissue model of the alveolus recently developed by the applicant. The use of fresh human cells from an ethically approved and verified source avoids contradictory results previously encountered using cell lines and any anomalies which might arise from using cells from other species. As well as understanding how HBHA contributes to the performance of Spore-FP1, our new lung model will be available to the scientific community for further studies of vaccine binding and translocation, helping reduce the number of animal experiments.
