A5030672021- HIV Research and Treatment
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- vaccines and immunoinformatics approaches
- Hepatitis B Virus Studies
Johns Hopkins University
2019-2024
Johns Hopkins Medicine
2021-2024
University of Baltimore
2019-2020
HIV-1 persists in a latent reservoir resting CD4+ T cells despite antiretroviral therapy (ART). The decays slowly over the first seven years of ART (t1/2 = 44 months). However, whether decay continues with long-term is unclear. Recent integration site studies indicate gradual selection against inducible, intact proviruses, raising speculation that decades might allow treatment interruption without viral rebound. Therefore, we measured 42 people on (mean 22 years) using quantitative outgrowth...
Background. Antiretroviral therapy (ART) halts HIV-1 replication, decreasing viremia to below the detection limit of clinical assays. However, some individuals experience persistent nonsuppressible (NSV) originating from CD4+ T cell clones carrying infectious proviruses. Defective proviruses represent over 90% all persisting during ART and can express viral genes, but whether they cause NSV complicate management is unknown.
Abstract The persistence of CD4 + T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics enhance HIV-1-specific immune responses and clear infected will probably be necessary achieve reduction reservoir. In present study, we report two single-chain diabodies (scDbs) that target HIV-1 envelope protein (Env) type III Fcγ receptor (CD16). We show scDbs promoted robust natural killer (NK) cell activation NK cell-mediated lysis...
HIV-1 infection is incurable due to the persistence of virus in a latent reservoir resting memory CD4+ T cells. “Shock-and-kill” approaches that seek induce gene expression, protein production, and subsequent targeting by host immune system have been unsuccessful lack effective latency-reversing agents (LRAs) kill strategies. In an effort develop reagents could be used promote killing infected cells, we constructed cell receptor (TCR)-mimic antibodies peptide-major histocompatibility...
During replication of some RNA viruses, defective particles can spontaneously arise and interfere with wild-type (WT) virus replication. Recently, engineered versions these interfering (DIPs) have been proposed as an HIV-1 therapeutic. However, DIPs yet to be reported in people (PWH). Here, we find PWH who a rare, polyclonal form non-suppressible viremia (NSV). While antiretroviral therapy (ART) rapidly reduces undetectable levels, individuals experience sustained due production from cell...
Summary Despite antiretroviral therapy (ART), HIV-1 persists in latently-infected CD4 + T cells, preventing cure. Antigens drive the proliferation of infected precluding latent reservoir decay. However, relationship between antigen recognition and gene expression is poorly understood since most studies latency reversal use agents that induce non-specific global cell activation. Here, we isolated rare cells responding to cytomegalovirus (CMV) or Gag antigens from participants on long-term ART...
Abstract The breadth and specificity of CD4+T cell responses in HIV-1 infection are critical determinants viral load an individual’s ability to control infection. Most studies against HIV have relied on indirect evidence from peptide-pulsing analyses. Direct antigen presentation been hampered by the technical difficulties inherent isolating peptide:MHC (p:MHC) complexes HIV-infected cells. This has made it challenging understand immunopeptidome, particularly for MHC-II epitopes. Using a...
Abstract HIV-1 infects CD4+ T cells and macrophages is currently incurable due to a latent reservoir. Targeting infected using TCR-mimic antibodies peptide-MHC (pMHC) would provide specific, high-affinity platform for immune system activation monitoring antigen processing. However, pMHC are notoriously difficult isolate. Using phage display platform, we panned expressing variable fragments against immunodominant HIV complexes. These Fab were cloned into bispecific antibody (bsAb) backbone,...