Background: During combined anti-retroviral treatment, a latent HIV reservoir persists within resting memory CD4 T cells that initiates viral recrudescence upon treatment interruption. Strategies for HIV-1 cure have largely focused on latency reversing agents (LRAs) capable of reactivating and eliminating this viral reservoir. Previously investigated LRAs have largely failed to achieve a robust latency reversal sufficient for reduction of latent HIV pool or the potential of virus-free remission in the absence of treatment.
Methods: We utilize a polyvalent virus-like particle (VLP) formulation called Activator Vector (ACT-VEC) to 'shock' provirus into transcriptional activity. Ex vivo co-culture experiments were used to evaluate the efficacy of ACT-VEC in relation to other LRAs in individuals diagnosed and treated during the acute stage of infection. IFN-γ ELISpot, qRT-PCR and Illumina MiSeq were used to evaluate antigenicity, latency reversal, and diversity of induced virus respectively.
Findings: Using samples from HIV patients diagnosed and treated at acute/early infection, we demonstrate that ACT-VEC can reverse latency in HIV infected CD4 T cells to a greater extent than other major recall antigens as stimuli or even mitogens such as PMA/Iono. Furthermore, ACT-VEC activates more latent HIV-1 than clinically tested HDAC inhibitors or protein kinase C agonists.
Interpretation: Taken together, these results show that ACT-VEC can induce HIV reactivation from latently infected CD4 T cells collected from participants on first line combined antiretroviral therapy for at least two years after being diagnosed and treated at acute/early stage of infection. These findings could provide guidance to possible targeted cure strategies and treatments.
Funding: NIH and CIHR.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502668 | PMC |
http://dx.doi.org/10.1016/j.ebiom.2020.102853 | DOI Listing |
Immunol Res
December 2024
Department of Respiratory Medicine, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.
This study aims to characterize the majority of immune cell subsets in peripheral blood mononuclear cells in children with Mycoplasma pneumoniae pneumonia (MPP) by a 21-color flow cytometry panel. Patients who met the predetermined eligibility criteria for pneumonia diagnosis were recruited for the research study. Multi-color flow cytometry was conducted on the peripheral blood mononuclear cells of each patient group, which were then subjected to dimensionality reduction and cluster analysis.
View Article and Find Full Text PDFmBio
December 2024
Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI), La Jolla, California, USA.
Frequent recent spillovers of subtype H5N1 clade 2.3.4.
View Article and Find Full Text PDFAdv Healthc Mater
December 2024
Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Although interest in peptide-based cancer vaccines has surged in the era of personalized immunotherapy enabled by the discovery of neoantigens, the effective generation of neoantigen-specific T cell responses has been limited. Here, a Brucella BP26 protein-based nanoparticle displaying the MHC class II-restricted melanoma neoantigen, M30, is reported for use as a therapeutic cancer vaccine. Genetic engineering of 10 tandem repeats of the M30 neoepitope to a BP26 monomer results in the self-assembled, neoantigen-displaying protein nanoparticles (BP26-M30 NPs).
View Article and Find Full Text PDFAnn Med
December 2025
Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Objective: This study aimed to observe the dynamic changes in the expression of T lymphocytes, natural killer (NK) cells, and PD-1 in patients with first-diagnosed esophageal squamous cell carcinoma (ESCC) before and after chemoradiotherapy (CRT) and evaluate the impact of PD-1 expression in peripheral blood on the short-term outcome of patients with ESCC.
Patients And Methods: Seventy-three patients with ESCC who were treated with definitive CRT were enrolled. Before and after CRT, flow cytometry was used to detect thePD-1 expression in the peripheral blood and related immune indicators.
J Inflamm Res
December 2024
Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.
Background: The aging of skin is a diversified biological phenomenon, influenced by a combination of genetic and environmental factors. However, the specific mechanism of skin photoaging is not yet completely elucidated.
Methods: Gene expression profiles for photoaging patients were obtained from the Gene Expression Omnibus (GEO) collection.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!