Dr Hyon-Xhi Tan
Hyon Xhi focuses on immunology, mainly investigating adaptive immune responses against respiratory viruses. He has a deep-rooted interest in the development of novel viral vaccines and combating diseases by harnessing our own immune system. Using a combination of precise microscopy imaging and flow cytometry, he examines factors that enhance B cell responses in mucosal tissues such as the lung, which can act as a first line of defence against recurring influenza or SARS-CoV-2 infections.
Respiratory viruses impose significant burden on human health through recurrent seasonal epidemics and periodic catastrophic pandemics. We face up to 500,000 deaths annually from Influenza infections, and the current COVID-19 pandemic already claiming over 4 million lives. Both diseases strikingly illustrate the critical need for highly effective vaccines and a better understanding of the immune system to protect susceptible human populations.
Development and characterisation of novel mucosal vaccines
Contemporary vaccines are primarily administered via muscular injections. However, mucosal tissues, such as the lung, are a primary route of entry for respiratory viral pathogens. Delivery of vaccines directly to the mucosal tissues may therefore constitute a strategy to improve immunity when and where it is most critically required during the initial phases of infection. We are exploring recombinant live-attenuated influenza vectors that are capable of delivering antigen directly to the lung mucosal tissue, with the aim of eliciting robust T and B cell responses locally within this tissue site.
Characterising humoral immunity in response to infection or vaccination
Vaccination and infection can drive vastly different immune outcomes, namely in the durability and magnitude of humoral responses. What similarities or differences underpin humoral immunity induced by infection or vaccination? Using recombinant probes, we are able to precisely interogate virus-specific B cells and dissect key phenotypes that correlate with a specific immune outcome. We also leverage next-generation sequencing to precisely define key transcriptional signatures of B cells that underpin robust humoral antibody responses.
Spike-specific B cells detected in individuals recovered from SARS-CoV-2 infection
Mucosal immunity and lung-resident B cells
The lung is a continual battleground between immune cells and invading respiratory viruses. While immune cells such as B cells are produced initially within secondary lymphoid organs (spleen, lymph nodes) upon infection or vaccination, these immune cells can subsequently migrate and lodge locally within the lung tissue. Once resident within tissues, these immune cells provide a rapid first-line of defence against recurrent infection by respiratory viruses. We examine and characterise immune factors that underpin migration of these cells to the non-lymphoid environment of the lung, and understand how specialised structures, such as the iBALT, are formed to facilitate retention of long-lived immune cells.
Specialised iBALT structures in lungs formed after influenza infection.