A5028344925- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- Herpesvirus Infections and Treatments
- HIV/AIDS Research and Interventions
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- HIV-related health complications and treatments
- Hepatitis C virus research
- Reproductive tract infections research
- Immune Response and Inflammation
- Animal Disease Management and Epidemiology
- Hepatitis B Virus Studies
- Virology and Viral Diseases
- Virus-based gene therapy research
- Blood groups and transfusion
- CAR-T cell therapy research
- Parvovirus B19 Infection Studies
- Mosquito-borne diseases and control
- bioluminescence and chemiluminescence research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
University of Alabama at Birmingham
2016-2025
Fred Hutch Cancer Center
2022
Birmingham VA Medical Center
2015
Office of Infectious Diseases
2014
California University of Pennsylvania
2013
DKFZ-ZMBH Alliance
1993-1997
German Cancer Research Center
1993-1997
Heidelberg University
1997
Gesundheitsamt
1993
Robert Koch Institute
1993
Defining the virus–host interactions responsible for HIV-1 transmission, including phenotypic requirements of viruses capable establishing de novo infections, could be important AIDS vaccine development. Previous analyses have failed to identify properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most these studies were limited examining envelope (Env) function in context pseudoviruses. Here, we...
ABSTRACT Genome sequences of transmitted/founder (T/F) HIV-1 have been inferred by analyzing single genome amplicons acute infection plasma viral RNA in the context a mathematical model random virus evolution; however, few these T/F molecularly cloned and biologically characterized. Here, we describe derivation biological analysis ten infectious molecular clones, each representing responsible for productive clade B clinical infection. Each viruses primarily utilized CCR5 coreceptor entry...
Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability viral envelope glycoproteins (Envs). To address these issues, suitable reference strains needed that representative global epidemic. Several panels have been recommended previously, but no clear answers available on how many which best suited for this purpose. We used a statistical model selection method to identify panel Env clones from among 219...
A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in community-based population Thailand (RV144 trial). No was observed Thai injection drug users who received AIDSVAX B/E alone (Vax003 We compared the neutralizing antibody response these 2 trials.
ABSTRACT Among nonneutralizing HIV-1 envelope antibodies (Abs), those capable of mediating antibody-dependent cellular cytotoxicity (ADCC) activity have been postulated to be important for control infection. ADCC-mediating Ab must recognize antigens expressed on the membrane infected cells and bind Fcγ receptor (FcR) effector cell population. However, precise targets serum ADCC antibody are poorly characterized. The human monoclonal (MAb) A32 is a isolated from an chronically person. We...
Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs prophylaxis therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, clade effects across different classes bNAbs. The defined variable loop 2 (V2) epitope HIV-1 Env were...
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...
Abstract Background Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, interferons (IFNs) are rapidly induced at sites of initial replication in the mucosa and draining lymph nodes. However, role played by IFN-stimulated antiviral activity restricting HIV-1 during stages infection is not clear. We hypothesized that if IFNs exert selective pressure on earliest infection, founder viruses succeed establishing systemic would be more IFN-resistant than replicating chronic...
Highlights•Macrophages selectively capture and engulf HIV-1-infected T cells•Uptake of cells drives efficient macrophage infection•T cell is viral Env independent; infection Env-receptor dependent•This represents a route for by transmitted/founder virusesSummaryMacrophages contribute to HIV-1 pathogenesis forming reservoir mediating neurological disorders. Cell-free macrophages inefficient, in part due low plasma membrane expression entry receptors. We find that CD4+ leading infection....
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells some encode envelope glycoproteins (Envs) contain fewer potential N-linked glycosylation sites...
Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed improve T cell-mediated clearance HIV-1-infected cells. Specifically, employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm was derived from broadly binding,...
Multispecific duoCAR-T cells potently suppress HIV infection in a humanized mouse model.
ABSTRACT Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit high-multiplicity autologous CD4 + T cells through viral envelope glycoprotein (Env) receptor- actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 LFA-1. Virological (VS)-mediated transmission MDM results high levels of cell integration 1 2...
ABSTRACT Control of HIV-1 replication following nonsterilizing vaccination could be achieved by vaccine-elicited CD8 + T-cell-mediated antiviral activity. To date, neither the functional nor phenotypic profiles T cells capable this activity are clearly understood; consequently, little is known regarding ability vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined T-cell subsets in combination with a highly standardized...
We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(-) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum antimicrobials, we hypothesized that CVL healthy (-) inhibit HIV infection.CVL 32 high CD4 counts 15 were collected by gently washing area 10 ml sterile normal saline. Following centrifugation, anti-HIV activity was determined incubating prior to addition TZM-bl cells. Antimicrobials...
Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of such antibodies remain incompletely understood. Furthermore, correlates between ADCC and HIV-1 immune status are not clearly defined. We screened the sera 20 HIV-1-positive (HIV-1(+)) patients for ADCC. Normal human peripheral blood mononuclear cells were used derive HIV-infected CD4(+) T cell targets autologous, freshly isolated, natural...
Natural killer (NK) cells with anti-HIV-1 activity may inhibit HIV-1 replication and dissemination during acute infection. We hypothesized that the capacity of NK to suppress in vivo infection would be augmented by activating them via treatment an interleukin-15 (IL-15) superagonist, IL-15 bound soluble IL-15Rα, approach potentiates human cell-mediated killing tumor cells. In vitro stimulation a recombinant superagonist significantly induced their expression cytotoxic effector molecules...
The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described influence infection epidemiological studies and regulate different immune responses that may affect infection, direct role female play altering susceptibility target cells HIV-infection is largely unknown. Here we evaluated effect 17-β-estradiol (E2) ethinyl estradiol (EE) CD4+ T-cells macrophages. Purified monocyte-derived macrophages were...
In the absence of an effective HIV-1 vaccine, passive immunization using broadly neutralizing Abs or Ab-like molecules could provide alternative to daily administration oral antiretroviral agents that has recently shown promise as preexposure prophylaxis. Currently, no single Ab (bNAb) combination bNAbs neutralizes all strains at practically achievable concentrations in vivo. To address this problem, we created bispecific combine inhibitory activity ibalizumab (iMab), a humanized mAb...
To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps identify which subsets of CD4+ support fusion productive infection. By comparing HIV-fused HIV-infected through dimensionality reduction, clustering, statistical approaches account for viral perturbations, identified a subset memory that entry but not gene expression. These express high levels CD127, the IL-7 receptor, are believed be...
HIV-1-infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surfaces are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated CD4-induced (CD4i) antibodies and sera from individuals (HIV+ sera). By downregulating surface expression of CD4, Nef prevents Env-CD4 interaction, thus protecting ADCC. HIV-1 infectious molecular clones (IMCs) widely used to measure In order facilitate identification infected high-throughput ADCC analysis,...