Institute: Liverpool School of Tropical Medicine
Biography
My research uses controlled human infection models (CHIMs) and advanced ex vivo systems to define immune correlates of protection and accelerate vaccine and therapeutic development. I have led CHIM studies on Salmonella Typhi and Streptococcus pneumoniae, identifying cellular predictors of protection and demonstrating how oral vaccination induces durable innate immune training.
Through translational models, I have revealed how HIV alters Mycobacterium tuberculosis replication and treatment response, and used lung organoids to explain why children are less susceptible to SARS-CoV-2. Current programmes include the CEPI-funded MUSICC consortium, Innovate UK’s Expedite SaVEP (self-amplifying vaccine acceleration), and AIR-HC, a £10M initiative automating high containment organoid infection models.
I supervise PhD students and postdoctoral researchers, contribute to global training initiatives, and am developing CHIMs for arboviruses such as Zika and Dengue. To date, my work has informed vaccine evaluation, therapeutic design, and public health policy, with a broader goal of advancing human-based models to reduce reliance on animals in infectious disease research.
Key Publications
1. Pennington, S. H., et al. 2016. Am J Respir Crit Care Med (IF 30.5). CHIM study showed memory B cells, not serum antibody, predict protection against pneumococcal carriage. Featured in editorial; redirected vaccine assessment towards cellular markers.
2. Pennington, S. H., et al. 2019. Sci Adv (IF 14.1). Demonstrated that live-attenuated oral vaccination (Ty21a) enhances innate defences, reducing all-cause mortality. Widely covered in media; informed vaccine policy discussions.
3. Jin, C., … Pennington, S. H., et al. 2019. PLoS Negl Trop Dis (IF 4.8). CHIM and intracellular models revealed suboptimal typhoid treatments contributing to resistance. Findings support novel therapies, including a combination strategy now in clinical trials.
4. Sposito, F., Pennington, S. H., et al. 2023. Mucosal Immunol (IF 7.3). Ex vivo airway organoids showed age-related epithelial factors limit SARS-CoV-2 in children. Provides mechanistic insight for targeted COVID-19 therapies.
5. Pennington, S. H., et al. 2022. J Infect Dis (IF 5.2). Intracellular co-infection model of HIV/TB revealed how HIV drives TB replication and alters therapy efficacy. Data advance understanding of pathogenesis and guide new treatments.
Web Links of Interest
https://www.lstmed.ac.uk/about/people/dr-shaun-pennington