The author provides a perspective on the global trends in emerging nanoscale vaccines for infectious diseases and describes the biological, experimental and logistical problems associated with their development, and how immunoengineering can be leveraged to overcome these challenges.
Mass spectrometry is used to identify 526 unique sequences from SARS-CoV-2 spike glycoprotein extracellular domain in a complex with human leukocyte antigen class II molecules on antigen presenting cells from a panel of healthy donors selected to represent a majority of allele usage from this highly polymorphic molecule.
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Researchers applied single-molecule Fluorescence Resonance Energy Transfer imaging to observe conformational dynamics of S on virus particles.
[Cell Host & Microbe]
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Lu, M., Uchil, P. D., Li, W., Zheng, D., Terry, D. S., Gorman, J., Shi, W., Zhang, B., Zhou, T., Ding, S., Gasser, R., Prévost, J., Beaudoin-Bussières, G., Anand, S. P., Laumaea, A., Grover, J. R., Liu, L., Ho, D. D., Mascola, J. R., … Mothes, W. (2020). Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles. Cell Host & Microbe, 0(0). https://doi.org/10.1016/j.chom.2020.11.001 Cite
Investigators showed that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans.
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Researchers analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, Western blotting and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from COVID-19 cases.
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Kusmartseva, I., Wu, W., Syed, F., Heide, V. V. D., Jorgensen, M., Joseph, P., Tang, X., Candelario-Jalil, E., Yang, C., Nick, H., Harbert, J. L., Posgai, A. L., Paulsen, J. D., Lloyd, R., Cechin, S., Pugliese, A., Campbell-Thompson, M., Heide, R. S. V., Evans-Molina, C., … Atkinson, M. A. (2020). Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19. Cell Metabolism, 0(0). https://doi.org/10.1016/j.cmet.2020.11.005 Cite
Initial studies have found increased severity of COVID-19, caused by infection with SARS-CoV-2, in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia.
[Nature Reviews Endocrinology]
Using multiple reagents and antibodies, the authors showed that ACE2 was expressed in human pancreatic islets, where it was preferentially expressed in subsets of insulin producing β-cells.
[Frontiers in Endocrinology]
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Fignani, D., Licata, G., Brusco, N., Nigi, L., Grieco, G. E., Marselli, L., Overbergh, L., Gysemans, C., Colli, M. L., Marchetti, P., Mathieu, C., Eizirik, D. L., Sebastiani, G., & Dotta, F. (2020). SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.596898 Cite
The authors employed human intestinal organoids derived from pluripotent stem cells to dissect SARS-CoV-2 pathogenesis and its inhibition by remdesivir, one of the leading drugs investigated for treatment of COVID-19.
[Cellular and Molecular Gastroenterology and Hepatology]
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Krüger, J., Groß, R., Conzelmann, C., Müller, J. A., Koepke, L., Sparrer, K. M. J., Weil, T., Schütz, D., Seufferlein, T., Barth, T. F. E., Stenger, S., Heller, S., Münch, J., & Kleger, A. (2020). Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2020.11.003 Cite
Scientists performed RNA structure probing to obtain single-base resolution secondary structure maps of the full SARS-CoV-2 coronavirus genome both in vitro and in living infected cells.
[Nucleic Acids Research]
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Manfredonia, I., Nithin, C., Ponce-Salvatierra, A., Ghosh, P., Wirecki, T. K., Marinus, T., Ogando, N. S., Snijder, E. J., van Hemert, M. J., Bujnicki, J. M., & Incarnato, D. (n.d.). Genome-wide mapping of SARS-CoV-2 RNA structures identifies therapeutically-relevant elements. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa1053 Cite
Researchers assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and showed that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with angiotensin converting enzyme-2 (ACE2) in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
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Investigators assessed the suitability of primary human bronchial epithelial cells maintained in air-liquid interface as an experimental system for studying SARS-CoV-2 infection in vitro.
[American Journal of Physiology-Lung Cellular and Molecular Physiology]
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