Research Report 2019_20


Han’s repertoire images are generated from data collected from an individual’s immune system. Each rectangle represents a unique T cell clone. Fewer and larger rectangles indicate less immune diversity. A diverse immune system is important to health and wellness.

When a new threat is introduced, the immune cells that recognize the invading pathogen multiply rapidly, causing a shift in the diversity of B cells or T cells. Han believes that by studying a person’s immune repertoire, scientists and clinicians can gain insights into what kind of immune cells will be effective at fighting off a disease or virus. To do this, Han and his team at HudsonAlpha developed next generation multiplex PCR technology, the arm-PCR method. The arm-PCR systems can eval- uate antibody and receptor rearrangement from a large number of cells at once by using hundreds of primers. Both iCubate and iRepertoire were founded upon the original arm-PCR method. Han and the iCubate team develop automated multiplex platforms that use single-use cassettes pre- loaded with all of the reagents necessary to perform a multiplex amplification and detection of infectious dis- eases in a sample. In 2019, iCubate received its second FDA-clearance for a test for the detection and identi- fication of potentially pathogenic bacteria associated with bloodstream infections and subsequent sepsis. The test, approved for detecting Gram-negative rod bacteria, works in concert with the previously approved test for detecting Gram-positive cocci bacteria to pro- vide a comprehensive bloodstream infection detection solution for clinical laboratories in the United States. In 2019 the group also published a study in the Journal of Biomedical Technology describing how the system can be used to rapidly detect and identify causative organisms and resistance markers of blood- stream infections 1 . Drawing on his successes as a scientist and entre- preneur, Han also has many years of experience using science and research to combat public health issues. Han was on the forefront of research during the SARS outbreak, H5N1, H1N1, H7N9 , and Zika virus.

Naturally, Han and his team began working on the SARS-CoV-2 virus as soon as it emerged. In a study published in the journal Frontiers in Immunology in September 2020, Han and collaborators in China used sequencing to characterize the immune system of patients who survived COVID-19 infection from symp- tom onset through recovery 2 . The study captured, for the first time, the expan- sion and contraction of all seven chains in the immune repertoire. The team discovered that early in COVID-19 infection, T cell discovery is significantly depleted. T cells recovered as patients improved, suggesting that the T cell repertoire might be an important marker for predicting disease progression. On the B cell side, the chain composition of receptors can indicate wheth- er the B cell has become “activated” by an infection. Activated B cells switch their chain type and begin pro- ducing antibodies. Determining which specific chains are activated might help identify what antibodies will be effective in treating the infection. Using this knowledge, iRepertoire is developing antibody-based treatments for COVID-19. By isolat- ing individual B cells that are exhibiting chain switch- ing, the team can identify the antibodies produced by patients who recover from SARS-CoV-2 infection. Han and the iRepertoire team have also been participating in a local study to use their single cell sequencing tech- nology on samples from infected patients by directly identifying SARS-CoV-2-specific B-cells. Both methods have revealed the identity of neutralizing antibodies that are being studied further for therapeutic potential. Han’s work shows the power of HudsonAlpha’s collaborative campus of public and private workspaces. The campus-wide environment facilitates opportunities for collaboration with more than 45 other companies that call HudsonAlpha’s campus home. n

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