T Cell Immune Discriminants of HIV Reservoir Size in a Pediatric Cohort of Perinatally Infected Individuals

Investigators demonstrated that T cell phenotypic signatures associate with viral reservoir size in a cohort of HIV vertically infected children and young adults under durable viral control, and who initiated anti-retroviral therapy under two years old.
[PLoS Pathogens]
Rinaldi, S., Armas, L. de, Dominguez-Rodríguez, S., Pallikkuth, S., Dinh, V., Pan, L., Gӓrtner, K., Pahwa, R., Cotugno, N., Rojo, P., Nastouli, E., Klein, N., Foster, C., Rossi, A. D., Giaquinto, C., Rossi, P., Palma, P., & Consortium, on behalf of E. (2021). T cell immune discriminants of HIV reservoir size in a pediatric cohort of perinatally infected individuals. PLOS Pathogens, 17(4), e1009533. https://doi.org/10.1371/journal.ppat.1009533 Cite
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Relationship of SARS-CoV-2-Specific CD4 Response to COVID-19 Severity and Impact of HIV-1 and Tuberculosis Co-Infection

Investigators assessed the magnitude, function and phenotype of SARS-CoV-2-specific CD4 T cells in 95 hospitalized COVID-19 patients and 38 non-COVID-19 patients, using flow cytometry.
[Journal of Clinical Investigation]
Riou, C., Bruyn, E. D., Stek, C., Daroowala, R., Goliath, R. T., Abrahams, F., Said-Hartley, Q., Allwood, B. W., Hsiao, N.-Y., Wilkinson, K. A., Arlehamn, C. S. L., Sette, A., Wasserman, S., & Wilkinson, R. J. (2021). Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and Tuberculosis co-infection. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI149125 Cite
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TTP-Mediated Regulation of mRNA Stability in Immune Cells Contributes to Adaptive Immunity, Immune Tolerance and Clinical App

Scientists summarize the effects of TTP-mediated regulation of mRNA stability in dendritic cells (DCs), focusing on DC maturation and antigen presentation, T cell activation and differentiation, immune tolerance and inflammation.
[RNA Biology]
Zhang, Y., Zhou, J., Wei, Z., Dong, H., Yang, D., Deng, Y., Li, J., Shi, S., Sun, Y., Lu, H., Yuan, J., Ni, B., Wu, Y., Tian, Y., & Han, C. (2021). TTP-mediated regulation of mRNA stability in immune cells contributes to adaptive immunity, immune tolerance and clinical applications. RNA Biology, 0(0), 1–7. https://doi.org/10.1080/15476286.2021.1917185 Cite
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Characterization of HIV-Induced Remodeling Reveals Differences in Infection Susceptibility of Memory CD4+ T Cell Subsets In Vivo

By applying bioinformatics analysis to mass cytometry-phenotyped specimens from individuals with viremia and in vitro-infected cells from uninfected donors, scientists provide an atlas of the phenotypes of in vivo and in vitro HIV-susceptible cells.
[Cell Reports]
Xie, G., Luo, X., Ma, T., Frouard, J., Neidleman, J., Hoh, R., Deeks, S. G., Greene, W. C., & Roan, N. R. (2021). Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4+ T cell subsets in vivo. Cell Reports, 35(4). https://doi.org/10.1016/j.celrep.2021.109038 Cite
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Automated Production of CCR5-Negative CD4+-T Cells in a GMP-Compatible, Clinical Scale for Treatment of HIV-Positive Patients

Investigators present a GMP-compatible mRNA electroporation protocol for the automated production of CCR5-edited CD4+-T cells in the closed CliniMACS Prodigy system.
[Gene Therapy]
Schwarze, L. I., Sonntag, T., Wild, S., Schmitz, S., Uhde, A., & Fehse, B. (2021). Automated production of CCR5 -negative CD4 + -T cells in a GMP-compatible, clinical scale for treatment of HIV-positive patients. Gene Therapy, 1–16. https://doi.org/10.1038/s41434-021-00259-5 Cite
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Human Anogenital Monocyte-Derived Dendritic Cells and langerin+cDC2 Are Major HIV Target Cells

Scientsts showed that HIV could penetrate the epithelial surface to interact with sub-epithelial resident mononuclear phagocytes in anogenital explants and defined the full array of subsets that were present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission.
[Nature Communications]
Rhodes, J. W., Botting, R. A., Bertram, K. M., Vine, E. E., Rana, H., Baharlou, H., Vegh, P., O’Neil, T. R., Ashhurst, A. S., Fletcher, J., Parnell, G. P., Graham, J. D., Nasr, N., Lim, J. J. K., Barnouti, L., Haertsch, P., Gosselink, M. P., Di Re, A., Reza, F., … Harman, A. N. (2021). Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells. Nature Communications, 12(1), 2147. https://doi.org/10.1038/s41467-021-22375-x Cite
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Lipid Nanoparticle Encapsulated Nucleoside-Modified mRNA Vaccines Elicit Polyfunctional HIV-1 Antibodies Comparable to Proteins in Nonhuman Primates

Researchers showed that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies.
[npj Vaccines]
Saunders, K. O., Pardi, N., Parks, R., Santra, S., Mu, Z., Sutherland, L., Scearce, R., Barr, M., Eaton, A., Hernandez, G., Goodman, D., Hogan, M. J., Tombacz, I., Gordon, D. N., Rountree, R. W., Wang, Y., Lewis, M. G., Pierson, T. C., Barbosa, C., … Haynes, B. F. (2021). Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates. Npj Vaccines, 6(1), 1–14. https://doi.org/10.1038/s41541-021-00307-6 Cite
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A Highly Multiplexed Droplet Digital PCR Assay to Measure the Intact HIV-1 Proviral Reservoir

Scientists designed two triplex droplet digital PCR assays, each with two unique targets and one in common, and normalize the results to PCR-based T cell counts.
[Cell Reports Medicine]
Levy, C. N., Hughes, S. M., Roychoudhury, P., Reeves, D. B., Amstuz, C., Zhu, H., Huang, M.-L., Wei, Y., Bull, M. E., Cassidy, N. A. J., McClure, J., Frenkel, L. M., Stone, M., Bakkour, S., Wonderlich, E. R., Busch, M. P., Deeks, S. G., Schiffer, J. T., Coombs, R. W., … Hladik, F. (2021). A highly multiplexed droplet digital PCR assay to measure the intact HIV-1 proviral reservoir. Cell Reports Medicine, 0(0). https://doi.org/10.1016/j.xcrm.2021.100243 Cite
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Neutrophil Subtypes Shape HIV-Specific CD8 T-cell Responses after Vaccinia Virus Infection

Scientists found that these neutrophil subtypes showed distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus infection.
[npj Vaccines]
Di Pilato, M., Palomino-Segura, M., Mejías-Pérez, E., Gómez, C. E., Rubio-Ponce, A., D’Antuono, R., Pizzagalli, D. U., Pérez, P., Kfuri-Rubens, R., Benguría, A., Dopazo, A., Ballesteros, I., Sorzano, C. O. S., Hidalgo, A., Esteban, M., & Gonzalez, S. F. (2021). Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection. Npj Vaccines, 6(1), 1–11. https://doi.org/10.1038/s41541-021-00314-7 Cite
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Curevo Vaccine Announces the Approval to Conduct a Phase Ib Clinical Trial in South Africa to Evaluate Safety and Immunogenicity of Its Adjuvanted Subunit Investigational Vaccine, CRV-101, Against Varicella (Chickenpox) in HIV-Positive Children

Curevo Vaccine announced that approval was granted to move forward with a Phase Ib pediatric clinical trial in South Africa to evaluate the safety, efficacy, and immunogenicity of its non-live investigational vaccine, CRV-101, against varicella in immunocompromised pediatric HIV-infected populations.
[Curevo Vaccine (BusinessWire, Inc)]
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Multi-Omics Analyses Reveal That HIV-1 Alters CD4+ T Cell Immunometabolism to Fuel Virus Replication

Scientists analyzed the transcriptome of CD4+ T cells from patients with HIV-1 and revealed that the elevated oxidative phosphorylation (OXPHOS) pathway is associated with poor outcomes.
[Nature Immunology]
Guo, H., Wang, Q., Ghneim, K., Wang, L., Rampanelli, E., Holley-Guthrie, E., Cheng, L., Garrido, C., Margolis, D. M., Eller, L. A., Robb, M. L., Sekaly, R.-P., Chen, X., Su, L., & Ting, J. P.-Y. (2021). Multi-omics analyses reveal that HIV-1 alters CD4 + T cell immunometabolism to fuel virus replication. Nature Immunology, 1–11. https://doi.org/10.1038/s41590-021-00898-1 Cite
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