A5001754141- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS Research and Interventions
- Gastrointestinal motility and disorders
- Congenital gastrointestinal and neural anomalies
- Digestive system and related health
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Gut microbiota and health
- HIV/AIDS drug development and treatment
- Blood groups and transfusion
- Complement system in diseases
- Mosquito-borne diseases and control
- Genetic Neurodegenerative Diseases
- Pancreatitis Pathology and Treatment
- Pancreatic function and diabetes
- Virology and Viral Diseases
- Virus-based gene therapy research
- Animal Disease Management and Epidemiology
- T-cell and B-cell Immunology
- Inflammation biomarkers and pathways
- Immunotherapy and Immune Responses
- Macrophage Migration Inhibitory Factor
- Adenosine and Purinergic Signaling
Johns Hopkins Medicine
2018-2024
Johns Hopkins University
2018-2024
23andMe (United States)
2024
Howard Hughes Medical Institute
2023
Significance The HIV-1 latent reservoir cannot be eradicated by antiretroviral therapy (ART). is a major barrier to cure. To characterize the mechanisms that contribute persistence of reservoir, we examined clonally expanded cell populations carrying replication-competent and followed them longitudinally. Expanded clones harboring were identified in all study participants, but these emerge wane on time scale years. A similar pattern was viruses sampled from residual viremia. findings suggest...
The eradication of the viral reservoir represents major obstacle to development a clinical cure for established HIV-1 infection. Here, we demonstrate that administration N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained control after discontinuation antiretroviral therapy (ART) simian-human AD8 (SHIV-AD8)-infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation transient viremia but only limited reductions SHIV...
Abstract The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control delayed rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- SHIV-infected rhesus macaques. Here we show combination active and passive immunization vesatolimod may lead to...
Abstract Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While formation begins during acute infection, mechanisms responsible for its establishment remain unclear. CD8 + T cells are important initial control viral replication. Here we examined effect on simian (SIV)-infected macaques by performing experimental depletion either before infection or early (that is,...
HIV-1 latency is a major barrier to cure. Identification of small molecules that destabilize and allow immune clearance infected cells could lead treatment-free remission. In vitro models involving cell lines or primary have been developed for characterization high-throughput screening latency-reversing agents (LRAs). We shown the majority LRAs identified date are relatively ineffective in from individuals despite activity model systems. show here that, diverse LRAs, reversal observed...
Abstract The establishment of a long-lived viral reservoir is the key obstacle for achieving an HIV-1 cure. However, anatomic, virologic, and immunologic features in tissues during antiretroviral therapy (ART) remain poorly understood. Here we present comprehensive necroscopic analysis SIV/SHIV multiple lymphoid non-lymphoid from SIV/SHIV-infected rhesus macaques suppressed with ART one year. Viral DNA observed broadly comparable animals that had initiated at week 1 or 52 infection. In...
Uncovering the sanctuaries of long-lived HIV-1 reservoir is crucial to develop cure strategies. Pediatric immunity distinct from that adults, which may alter where established in infancy. Thus, it important utilize pediatric models inform cure-directed approaches for HIV-1-infected children. We used an infant rhesus macaque model infection via breastfeeding identify key sites viral persistence under antiretroviral therapy (ART). The gastrointestinal tract was found be a site low-level...
The enteric nervous system (ENS), a collection of neural cells contained in the wall gut, is fundamental importance to gastrointestinal and systemic health. According prevailing paradigm, ENS arises from progenitor migrating crest remains largely unchanged thereafter. Here, we show that lineage composition maturing changes with time, decline canonical neural-crest derived neurons their replacement by newly identified mesoderm-derived neurons. Single cell transcriptomics immunochemical...
The enteric nervous system (ENS), a collection of neural cells contained in the wall gut, is fundamental importance to gastrointestinal and systemic health. According prevailing paradigm, ENS arises from progenitor migrating crest remains largely unchanged thereafter. Here, we show that lineage composition maturing changes with time, decline canonical neural-crest derived neurons their replacement by newly identified mesoderm-derived neurons. Single cell transcriptomics immunochemical...
While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, is not always possible postnatal pediatric HIV infections. The timing ART likely to affect size latent viral reservoir established, as development adaptive immune responses, such generation neutralizing antibody responses against virus. How these parameters impact ability control viremia and time rebound after interruption unclear has never been modeled infants. To...
Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective HIV-1 cure research. In this study, we investigated the therapeutic efficacy vaccine consisting adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without SIV Envelope (Env) gp140 protein alum adjuvant combination TLR7 agonist vesatolimod (GS-9620) 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA vaccination led to...
The latent reservoir for HIV-1 in resting CD4 + T cells persists despite antiretroviral therapy (ART) and precludes cure. Reservoir-targeting interventions are evaluated ART-treated macaques infected with simian immunodeficiency virus (SIV) or simian-human (SHIV). Efficacy is determined by measurements before after the intervention. However, most proviruses persisting setting of ART defective. In addition, intact SIV genomes undergo complex, multiphasic decay observable when new infection...
Abstract Viral dynamics of acute HIV infection and rebound following suspension antiretroviral therapy may be qualitatively similar but must differ given, for one, development adaptive immune responses. Understanding the differences viral in pediatric populations provide insights into mechanisms control with potential implications vaccine design effective targeted therapeutics infants children. Mathematical models have been a crucial tool to elucidate complex processes driving infections...
While memory T-cells represent a hallmark of adaptive immunity, little is known about the genetic mechanisms regulating longevity CD4 T cells. Here, we studied dynamics gene expression in antigen specific cells during infection, differentiation, and long-term survival up to nearly year mice. We observed that differentiation into long lived associated with increased genes inhibiting cell proliferation apoptosis as well promoting DNA repair response, lipid metabolism, insulin resistance....
A bstract While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, ART is not always possible postnatal pediatric HIV infections, which account for majority cases worldwide. The timing onset likely to affect size latent viral reservoir established, as development adaptive immune responses, such generation neutralizing antibody responses against virus. How these parameters impact ability control viremia and time rebound after...
Abstract The enteric nervous system (ENS), a collection of neural cells contained in the wall gut, is fundamental importance to gastrointestinal and systemic health. According prevailing paradigm, ENS arises from progenitor migrating crest remains largely unchanged thereafter. Here, we show that lineage composition maturing changes with time, decline canonical neural-crest derived neurons their replacement by newly identified mesoderm-derived neurons. Single cell transcriptomics...
Abstract 23ME-00610 is a monoclonal antibody that being evaluated as single agent in Phase 1/2a clinical trial for advanced solid malignancies (NCT05199272). It binds with high affinity (KD < 0.1 nM) to CD200R1, promising immune-oncology (IO) target identified by surveying the 23andMe genetic and health survey database. CD200R1 an inhibitory receptor when bound its ligand CD200, reduces pro-inflammatory cytokine production, leads immunosuppressive tumor environment. To gain further...
A bstract The presence of antibodies against HIV in infected children is associated with a greater capacity to control viremia the absence therapy. While benefits early antiretroviral treatment (ART) infants are well documented, ART may interfere development antibody responses. In contrast adults, treated lack detectable HIV-specific antibodies, suggesting fundamental difference pathogenesis. Despite this potential adverse effect, decrease size latent reservoir established infection infants,...
The enteric nervous system (ENS), a collection of neural cells contained in the wall gut, is fundamental importance to gastrointestinal and systemic health. According prevailing paradigm, ENS arises from progenitor migrating crest remains largely unchanged thereafter. Here, we show that lineage composition maturing changes with time, decline canonical neural-crest derived neurons their replacement by newly identified mesoderm-derived neurons. Single cell transcriptomics immunochemical...