Self-Amplifying RNA Vaccines for Infectious Diseases

Scientists explore how self-amplifying RNAs are emerging as important vaccine candidates for infectious diseases, the advantages of synthetic manufacturing approaches, and their potential for preventing and treating chronic infections.
[Gene Therapy]
Bloom, K., van den Berg, F., & Arbuthnot, P. (2020). Self-amplifying RNA vaccines for infectious diseases. Gene Therapy, 1–13. https://doi.org/10.1038/s41434-020-00204-y Cite
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HIV-1 Env Induces Pexophagy and an Oxidative Stress Leading to Uninfected CD4+ T Cell Death

Scientists demonstrated that envelope glycoproteins (Env)-induced oxidative stress was responsible for their death by apoptosis. Moreover, they report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy.
[Autophagy]
Daussy, C. F., Galais, M., Pradel, B., Robert-Hebmann, V., Sagnier, S., Pattingre, S., Biard-Piechaczyk, M., & Espert, L. (2020). HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4+ T cell death. Autophagy, 0(0), 1–10. https://doi.org/10.1080/15548627.2020.1831814 Cite
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Laboratory-Scale Lentiviral Vector Production and Purification for Enhanced Ex Vivo and In Vivo Genetic Engineering

Researchers describe an optimized laboratory-scale workflow whereby lentiviral vector (LV)-containing supernatant was purified and concentrated by sequential chromatographic steps, obtaining biologically active LVs with infectious titer and specific activity in the order of 109 Transducing Unit (TU)/ml and 5×104 TU/ng of HIV Gag p24, respectively.
[Molecular Therapy-Methods & Clinical Development]
Soldi, M., Sergi, L. S., Unali, G., Kerzel, T., Cuccovillo, I., Capasso, P., Annoni, A., Biffi, M., Rancoita, P. M. V., Cantore, A., Lombardo, A., Naldini, L., Squadrito, M. L., & Kajaste-Rudnitski, A. (2020). Laboratory-scale lentiviral vector production and purification for enhanced ex vivo and in vivo genetic engineering. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2020.10.009 Cite
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Orion Biotechnology Successfully Completes Phase I Clinical Trial of a First-in-Class Precision Engineered Ligand Analog for HIV Prevention

Orion Biotechnology Canada Ltd. announced the results of their Phase I study of OB-002H which is an investigational candidate microbicide for HIV prevention.
[Orion Biotechnology Canada Ltd.]
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Maternal HIV Status Skews Transcriptomic Response in Infant Cord Blood Monocytes Exposed to BCG

HIV-unexposed (HU) and HIV-exposed uninfected (HEU) infant cord blood monocytes were treated with Bacillus Calmette-Guerín (BCG) and transcriptionally profiled with the Nanostring nCounter platform. Differential expression and pathway enrichment analyses were performed, and transcripts were identified with enhanced or dampened BCG responses.
[AIDS]
Jones, C. I., Rose, S. L., Shutt, A., Cairo, C., Bourgeois, N. M., Charurat, M., Sodora, D. L., & Wood, M. P. (2020). Maternal HIV status skews transcriptomic response in infant cord blood monocytes exposed to BCG. AIDS, Publish Ahead of Print. https://doi.org/10.1097/QAD.0000000000002706 Cite
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Transcriptional Regulation of Memory B Cell Differentiation

The authors discuss recent advancements regarding the signals and transcription factors regulating germinal centre-derived memory B cells development and function.
[Nature Reviews Immunology]
Laidlaw, B. J., & Cyster, J. G. (2020). Transcriptional regulation of memory B cell differentiation. Nature Reviews Immunology, 1–12. https://doi.org/10.1038/s41577-020-00446-2 Cite
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Reconstitution and Visualization of HIV-1 Capsid-Dependent Replication and Integration In Vitro

Scientists reconstituted processes of reverse transcription and concerted integration in a cell-free system, using purified HIV-1 virions as the source of viral genomes and enzymes.
[Science]
Christensen, D. E., Ganser-Pornillos, B. K., Johnson, J. S., Pornillos, O., & Sundquist, W. I. (2020). Reconstitution and visualization of HIV-1 capsid-dependent replication and integration in vitro. Science, 370(6513). https://doi.org/10.1126/science.abc8420 Cite
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The lncRNA LOC102549805 (U1) Modulates Neurotoxicity of HIV-1 Tat Protein

Scientists discovered that exposure of rat primary neurons to Tat resulted in the up-regulation of an uncharacterized long non-coding RNA (lncRNA), LOC102549805.
[Cell Death & Disease]
Torkzaban, B., Natarajaseenivasan, K., Mohseni Ahooyi, T., Shekarabi, M., Amini, S., Langford, T. D., & Khalili, K. (2020). The lncRNA LOC102549805 (U1) modulates neurotoxicity of HIV-1 Tat protein. Cell Death & Disease, 11(10), 1–12. https://doi.org/10.1038/s41419-020-03033-4 Cite
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The HIV-1 Latent Reservoir Is Largely Sensitive to Circulating T Cells

Scientists investigated the patterns of T cell escape variants in the replication-competent reservoir of 25 persons living with HIV-1 durably suppressed on ART.
[eLife]
Warren, J. A., Zhou, S., Xu, Y., Moeser, M. J., MacMillan, D. R., Council, O., Kirchherr, J., Sung, J. M., Roan, N., Adimora, A. A., Joseph, S., Kuruc, J. D., Gay, C. L., Margolis, D. M., Archin, N., Brumme, Z. L., Swanstrom, R., & Goonetilleke, N. (2020). The HIV-1 latent reservoir is largely sensitive to circulating T cells. ELife, 9, e57246. https://doi.org/10.7554/eLife.57246 Cite
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HIV Antivirals Affect Endothelial Activation and Endothelial-Platelet Crosstalk

HUVECs or human coronary artery endothelial cells were pre-treated with the antiretrovirals abacavir sulphate, tenofovir disoproxil fumarate or tenofovir alafenamide.
[Circulation Research]
Khawaja Akif A, Taylor Kirk A, Lovell Andrew O, Nelson Mark, Gazzard Brian, Boffito Marta, & Emerson Michael. (n.d.). HIV Antivirals Affect Endothelial Activation and Endothelial-Platelet Crosstalk. Circulation Research, 0(0). https://doi.org/10.1161/CIRCRESAHA.119.316477 Cite
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$111 Million NIH Grant Awarded to Prevent and Treat HIV-Associated Cancers

Montefiore Health System and Albert Einstein College of Medicine have received a five-year, $111 million grant from the National Cancer Institute to lead this research consortium.
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