- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Wound Healing and Treatments
- Dermatologic Treatments and Research
- Cytomegalovirus and herpesvirus research
- Transgenic Plants and Applications
- Surgical Sutures and Adhesives
- HIV/AIDS drug development and treatment
Henry M. Jackson Foundation
2014-2018
Walter Reed Army Institute of Research
2014-2018
Oregon Health & Science University
2012-2016
Oregon National Primate Research Center
2013-2016
University of Miami
2008
Vollum Institute
2008
Human immunodeficiency virus, type 1, negative factor (Nef) initiates down-regulation of cell-surface major histocompatibility complex-I (MHC-I) by assembling an Src family kinase (SFK)-ZAP70/Syk-phosphoinositide 3-kinase (PI3K) cascade through the sequential actions two sites, Nef EEEE<sup>65</sup> and P<i>XX</i>P<sup>75</sup>. The internalized MHC-I molecules are then sequestered in endosomal compartments a process requiring Met<sup>20</sup>. How assembles multikinase to trigger pathway is...
Delineating the key early events that lead to development of broadly neutralizing anti-HIV-1 antibodies during natural infection may help guide immunogens and vaccine regimens prevent HIV-1 infection. In this study, we monitored two HIV-1-positive subjects, VC20013 VC10014, over course from before they developed antibody (bNAb) activity until several years after breadth was detected in plasma. Both subjects bNAb approximately 1 year postinfection, which ultimately mapped membrane-proximal...
Abstract Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV efficacy. Vaccine-elicited responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses establish humans. Most candidates date been ineffective at generating Abs neutralize T/F or early variants. In this study, we report coimmunizing rhesus macaques with HIV-1 gp160 DNA...
ABSTRACT Effector CD4 T cell responses have been shown to be critically involved in the containment and clearance of viral pathogens. However, their involvement pathogenesis HIV infection is less clear, given additional role as preferred targets. We previously demonstrated that presence HIV-specific somewhat associated with control specific functions, such direct cytolytic activity, can contribute viremia. little known about how induction during acute influences disease progression whether...
Abstract The importance of Fc-dependent effector functions Abs induced by vaccination is increasingly recognized. However, mice against HIV envelope (Env) a skewed Th cell response leading to Env-specific with reduced function. To overcome this bias, GagPol-specific cells were harnessed provide intrastructural help for B after immunization virus-like particles containing GagPol and Env. This led balanced humoral immune more inflammatory Fc glycan profile. increased quality in the Ab Env was...
Identifying characteristics of the human immunodeficiency virus type 1 (HIV-1) envelope that are effective in generating broad, protective antibodies remains a hurdle to HIV vaccine design. Emerging evidence development broad and potent neutralizing HIV-infected subjects suggests founder subsequent progeny viruses may express unique antigenic motifs contribute this developmental pathway. We hypothesize over course natural infection, B cells programmed develop by exposure select populations...
The maturation process of high-affinity antibodies is a result intricate interactions between B cells and follicular helper T (Tfh) occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, inflammation driven by years continuous viral replication. High levels viremia as well activation dysfunction have been demonstrated to perturbing impact on the cell memory compartment contribute exhaustion. Counterintuitively, factors...
To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E (RV144 trial) has demonstrated protection, albeit modestly (31%; P = 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although cells, particularly follicular helper (Tfh) are critical effective antibody responses, most...
Background HIV-1 evolves rapidly within the host, resulting in development of diverse variants called a viral “quasispecies” population. A major goal vaccine efforts is design Envelope (Env)-based immunogens effective at eliciting broadly neutralizing antibodies. We hypothesize that B cells become programmed to develop broad NAbs by exposure Envs presented quasispecies variants. propose similar programming could be achieved concept exposing host such Env isolated from an individual who...
Background: Bilayered cell therapy (BLCT) is a significant advancement in the field of wound healing. BLCT expresses multiple growth factors found normal skin, and provides biologically active matrix chronic wounds. Antibiotic-resistant bacterium continues to be major problem The use appropriate topical antimicrobial agents could one first steps prevention infection, although their with limited due reported toxicity cultured keratinocytes. Objectives: This study was designed see whether...