A5029754146- HIV Research and Treatment
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Virus-based gene therapy research
- T-cell and Retrovirus Studies
- Immune cells in cancer
- Herpesvirus Infections and Treatments
- vaccines and immunoinformatics approaches
- Glioma Diagnosis and Treatment
- Animal Disease Management and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous Melanoma Detection and Management
- Single-cell and spatial transcriptomics
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Hepatitis B Virus Studies
- Immunodeficiency and Autoimmune Disorders
- Mathematical Biology Tumor Growth
Duke University Health System
2025
Duke Cancer Institute
2024-2025
Duke Medical Center
2014-2024
Duke University
2014-2024
Duke University Hospital
2004-2022
Nanostring Technologies (United States)
2019
University of North Carolina at Chapel Hill
2015
Università Cattolica del Sacro Cuore
2015
University Hospitals of Cleveland
2015
Case Western Reserve University
2015
The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated (LAV). In this report, we describe the antiviral effects thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as triphosphate, inhibits reverse transcriptase HTLV-III/LAV. This agent blocks expression p24 gag protein HTLV-III/LAV in H9 following exposure virus. drug also cytopathic...
The thymidine analog 3'-azido-3'-deoxythymidine (BW A509U, azidothymidine) can inhibit human immunodeficiency virus (HIV) replication effectively in the 50-500 nM range [Mitsuya, H., Weinhold, K. J., Furman, P. A., St. Clair, M. Nusinoff-Lehrman, S., Gallo, R. C., Bolognesi, D., Barry, D. W. & Broder, S. (1985) Proc. Natl. Acad. Sci. USA 82, 7096-7100]. In contrast, inhibition of growth uninfected fibroblasts and lymphocytes has been observed only at concentrations above 1 mM. nature this...
The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part a disulfide bridged loop in the third variable region external envelope protein, gp120. Analysis amino acid sequences this domain from 245 different isolates revealed that PND less than thought originally. Conservation to better 80 percent acids 9 out 14 positions central portion and occurrence particular oligopeptide majority suggest there are constraints on variability. One constraining influence may...
Identification of the transmitted/founder virus makes possible, for first time, a genome-wide analysis host immune responses against infecting HIV-1 proteome. A complete dissection was made primary HIV-1–specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites positive selection genome, showed that cells rapidly select escape mutations concurrent falling load acute infection. Kinetic and mathematical modeling...
A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment transmission through establishment latent pool HIV-1-infected cells. critical time study initial transmitted/founder is eclipse phase HIV-1 infection (time first appearance plasma virus), but, date, this period has been logistically difficult analyze. To probe B-cell immediately following transmission, we have determined envelope-specific antibody autologous and...
Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation multiple immune checkpoints, known contributor to failures amid checkpoint blockade, strategy that has lacked success thus far GBM. This study among first examine, credential as bona fide, T cells infiltrating human murine GBM.Experimental Design: Tumor-infiltrating...
Immunization with either an Escherichia coli recombinant segment of the human T-cell lymphotropic virus (HTLV-III/LAV) envelope protein (gp120) or deglycosylated gp120 produced antibodies that neutralize HTLV-III/LAV infection in vitro. Virus neutralization titers these antisera were equivalent to those obtained purified native as immunogen. This localizes at least one class neutralizing epitopes carboxyl-terminal half molecule. In addition, prevented HTLV-III/LAV—mediated cell fusion,...
Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, whether improves survival has not been established.
Reverse transcriptase was purified from human immunodeficiency virus (HIV). It utilized the artificial primer-template poly(rA)-oligo(dT)12-18 more efficiently than activated calf thymus DNA, poly(rI)-oligo(dC)12-18, poly(rC)-oligo(dG)12-18, or poly(rCm)-oligo(dG)12-18. Maximum activity observed at pH 7.0 to 7.6 in presence of 5 mM MgCl2 and 100 KCl. 3'-Azido-3'-deoxythymidine triphosphate competed with dTTP for binding HIV reverse transcriptase. Different kinetic constants were obtained...
Abstract Background Cytokine flow cytometry (CFC) or intracellular cytokine staining (ICS) can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity different candidates across multiple international organizations conducting clinical trials. As such, study was carried out several involved HIV trials, define inter-lab...
A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable destroying virally infected targets. Recent application recombinant canarypox ALVAC/HIV-1 vectors as immunogens in HIV-1,-noninfected volunteers has produced CTL responses a significant number vaccinees. Using newly developed targeting strategy, we examined capacity vaccine-induced lyse autologous targets with diverse group...
The magnitude of immunologic defects observed in HIV-1-infected individuals before the development overt AIDS is disproportionately high comparison to levels infectious virus these patients--suggesting that factors other than direct virus-induced cytopathology may be involved. With this mind, we investigated consequences interaction between purified HIV-1 gp120 and CD4 molecules expressed by uncommitted as well Ag-specific lymphocytes. exhibited a dose-dependent immunosuppressive effect on:...
Abstract We have developed a high‐throughput platform to detect the presence of HIV‐1 and SIV‐specific ADCC‐mediating antibody responses. The assay is based on hydrolysis cell‐permeable fluorogenic peptide substrate containing sequence recognized by serine protease, Granzyme B (GzB). GzB delivered into target cells cytotoxic effector as result antigen (Ag)‐specific Ab‐Fcγ receptor interactions. Within cells, cell‐derived hydrolyzes substrate, generating fluorescent signal that allows...
A key question in understanding the status of immune system HIV-1 infection is whether adult thymus contributes to reconstitution peripheral T lymphocytes. We analyzed patients who died infection. In addition, we studied clinical course three thymectomized for myasthenia gravis and determined effect antiretroviral therapy on CD4(+) cells. found that five seven had tissue at autopsy all thymuses identified inflammatory infiltrates surrounding lymphodepleted thymic epithelium. Two also areas...
A safety and immunogenicity trial was conducted in vaccinia-immune vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN gp160 10(5.5) ALVAC-rabies glycoprotein control at 0 1 2 months ALVAC-gp160 50 microg HIV-1SF2 recombinant (r) gp120 microfluidized emulsion 9 12 months; others received rgp120 0, 1, 6, months. All vaccines well-tolerated. Neither status before vaccination nor...
Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV as tumor-specific immunotherapy targets. A recent trial recurrent patients demonstrated the potential clinical benefit of adoptive T-cell therapy (ATCT) phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change capacity pp65-specific cells gain multiple...
Induction of CD8+ cytotoxic T cells is considered one the important correlates for protective efficacy candidate human immunodeficiency virus type 1 (HIV-1) vaccines. To induce lymphocytes (CTLs) along with neutralizing antibody and CD4+ cell help, a live canarypox construct expressing gp120, transmembrane gp41, gag protease genes, sequences containing CTL epitopes in nef pol was given simultaneously with, or followed by, rgp120 SF2. CTLs were detected 61% volunteers at some time during...
Objective: To determine the ability of live attenuated canarypox virus expressing HIV antigens to induce CD8+ cytotoxic T-cell responses and prime for neutralizing antibody boosting with purified recombinant gp120 subunit vaccine. Design: A prospective, double-blind, randomized, immunogenicity safety study was conducted in healthy adults at low risk acquiring infection who were seronegative HIV. Methods: T-cells directed against Env or Gag target cells measured after canarypox-HIV-1 vaccine...
Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely have either natural or acquired resistance the virus. We studied four such uninfected cohorts, representing 60 individuals, evidence of protective immunity. This included participants HIV through anal vaginal receptive intercourse on multiple occasions over many years. observed CD8 + -cell noncytotoxic inhibition replication in acutely infected CD4 cells vast majority individuals...
Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers without gp120 boosting, expand the safety database compare immunogenicity of who were at higher risk lower for Neutralizing antibodies MN strain stimulated 94% given vCP205 plus 56% alone. CD8+ cytotoxic T...
Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of cell-mediated immune have been identified. Here, we examine in a HLA-B27 + HIV seronegative vaccinee persistent vaccine-induced anti-Gag CD4 and CD8 responses. Although these exhibited those characteristics (multifunctionality, appropriate memory phenotype, targeting epitopes associated with long-term...
We have studied the biologic and physical properties of a monoclonal antibody that binds to gp120, exterior envelope glycoprotein human immunodeficiency virus (HIV) strain HTLV-IIIB. Designated 9284, possesses viral neutralizing activity inhibits syncytium formation by infected cells. The recognized region polypeptide backbone previously described as an important epitope. This lies 307-330 residues from amino terminus glycoprotein. compared this those recently 0.5β gp120. was biologically...
Cytophilic antibodies which mediate antibody dependent cellular cytotoxicity (ADCC) against envelope antigens of human immunodeficiency virus (HIV) can be found in seropositive individuals. In these experiments, sera from a wide spectrum HIV infected patients ranging asymptomatic to overt acquired syndrome (AIDS) were shown contain high titers that ADCC. Not only did patient bind surface expressed viral and ADCC cells chronically with T-lymphotropic type IIIB (HTLV-IIIB), but also the...