CONGRESS 2023 - Controlled Human Infection Models: Anti-viral immunity in the respiratory tract

Controlled human infection models (CHIMs) allow researchers to deliberately infect volunteers with a carefully pre-defined viral inoculum and perform detailed investigations. These can examine both pre-existing immune responses and allow longitudinal sampling of multiple immunological compartments following infection. The unique nature of these CHIMs avoid the multiple confounding factors, which tend to limit conventional observational studies of naturally acquired viral infections in patients. We have successfully established challenge models of influenza (H1N1 and H3N2), Respiratory Syncytial Virus (RSV) and SARS-CoV2, and used a variety of tools (such as multi-parameter flow cytometry, ELISpot, multiplex cytokine and chemokine arrays and transcriptomics) to characterise populations of low-frequency virus-specific CD4+ and CD8+ T cells in both peripheral blood and cells in the upper and lower airways from challenge participants. We have also been able to extend our infection models into vulnerable populations, such as older adults, and use these techniques to investigate fundamental questions about the kinetics, specificities, and functionality of the cell-mediated response in these clinically relevant populations. Challenge models allow us to probe the immune response to respiratory viral infections in a uniquely detailed manner. These advantages also make challenge models an attractive approach to testing the efficacy of novel vaccines and vaccine platforms, potentially leading to new vaccines and therapeutics, able to generate robust anti-viral immunity, while avoiding the significant risks and costs associated with traditional Phase II/III vaccine trials.

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