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Biology subjects

Sun, A. Y.

Publications and source records attributed to Sun, A. Y..

3 recordsLinked to original sources

A new mRNA antigen vaccine induces potent B and T cell responses and in vivo protection against SARS-CoV-2

The SARS-CoV-2 mRNA vaccine provides effective protection against viral infection and severe disease by inducing efficient adaptive immunity. However, vaccine efficacy is decreased against emerging variants, and immune memory is relatively short-lived. Here, we added new T cell epitopes to the RBD (receptor-binding domain) mRNA vaccine and identified a SARS-CoV-2 membrane epitope that significantly improved vaccine-induced immunity and protection in vivo. That new vaccine, designated G1-C, induced 8.2-fold higher levels of RBD-specific antibodies than did RBD and enhanced spike-specific T cell and B cell responses. Remarkably, the G1-C modulated hematopoietic stem cell (HSC) differentiation and increased levels of B and NK cells by regulating multiple signaling pathways in bone marrow potentially via Fos, Klf4, and Klf6 transcription factors. Altogether, these findings identify a new vaccine candidate to control viral infection by affecting the lymphoid-myeloid lineage bias and suggest the potential role of T cell epitopes in vaccine design and development.

immunology↗

Single Cell Analysis of pBMCs of Psoriasis patients reveals distinct CD4+ T cell phenotypes associated with response to IL-23 blockade.

The use of IL-23 inhibitors (IL-23i) for psoriatic diseases has resulted in significant improvement in disease symptoms for many patients. The extent of disease improvement following IL-23 blockade varies across patients with psoriasis; however, the immunologic factors associated with a good or poor response to IL-23 blockade remain unclear. Here, we utilized peripheral blood mononuclear cells (pBMCs) collected through the MINIMA clinical trial (NCT04271540) and applied single-cell RNA sequencing to profile circulating immune populations from 27 patients with psoriasis or psoriatic arthritis, aiming to identify cellular features associated with a response to IL-23 blockade. We identified populations of CD4+ T cells whose abundance in circulation before treatment was associated with improved skin disease following IL-23i treatment. Circulating CD4+ T cells that demonstrate transcriptomic features of Th1-like cells were associated with better psoriasis skin improvement and had transcriptomic signatures resembling T cells identified in psoriasis lesional skin. Further, decrease in levels of IL-17A and IFN{gamma} in serum each correlated with improvement in PASI levels. These results suggest that immune cell features detectable in blood may be informative in identifying patients with psoriasis who are likely to have a robust clinical response to IL-23 blockade.

immunology↗

Democratizing access to microfluidics: Rapid prototyping of capillary microfluidics with a low-cost masked stereolithography 3D printer

Microfluidics offer user-friendly liquid handling for a range of biochemical applications. 3D printing microfluidics is rapid and cost-effective compared to conventional cleanroom fabrication. Typically, microfluidics are 3D printed using digital light projection (DLP) stereolithography (SLA), but many models in use are expensive ([&ge;]$10,000 USD), limiting widespread use. Recent liquid crystal display (LCD) technology advancements have provided inexpensive (<$500) SLA 3D printers with sufficient pixel resolution for microfluidic applications. However, there are only a few demonstrations of microfluidic fabrication, limited validation of print fidelity, and no direct comparisons between LCD and DLP printers. We compared a 40 {micro}m pixel resolution DLP printer ([~]$18,000 USD) with a 34.4 {micro}m (<$380) LCD-SLA printer. Consistent with prior work, we observed linear trends between designed and measured channel widths [&ge;] 4 pixels on both printers, so we calculated accuracy above this size threshold. Using a standard IPA wash resin and optimized parameters for each printer, the average error between designed and measured widths was 2.11 {+/-} 1.26% with the DLP printer and 15.4 {+/-} 2.57% with the 34.4 {micro}m LCD printer. The average coefficient of variation [CV] was [~]2% for both printers. Printing with optimized conditions for a low-cost water wash resin designed for LCD-SLA printers resulted in an average error of 2.53 {+/-} 0.94% with the 34.4 {micro}m LCD printer and 5.35 {+/-} 4.49% with a 22 {micro}m LCD printer. We characterized additional parameters including surface roughness, channel perpendicularity, and light intensity uniformity, and as an application of LCD-printed devices, we demonstrated consistent flow rates in capillaric circuits for self-regulated and self-powered delivery of multiple liquids. In conclusion, LCD printers are an inexpensive alternative for fabricating microfluidics, with minimal differences in fidelity and accuracy compared with a 20X more expensive DLP printer.

scientific communication and education↗