A5070179322- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Immune responses and vaccinations
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Tuberculosis Research and Epidemiology
- HIV/AIDS oral health manifestations
- Galectins and Cancer Biology
- interferon and immune responses
- Acute Lymphoblastic Leukemia research
- Oral Health Pathology and Treatment
- CAR-T cell therapy research
- Liver Diseases and Immunity
- Organ Transplantation Techniques and Outcomes
- Oral microbiology and periodontitis research
- Cytokine Signaling Pathways and Interactions
- Liver Disease and Transplantation
- Virology and Viral Diseases
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
Baylor College of Medicine
2023
Texas Children's Hospital
2023
Methodist Hospital
2018-2023
Emory University
2007-2019
Houston Methodist
2017-2018
Methodist Hospital
2017
Emory National Primate Research Center
2007-2010
Emory Healthcare
2007
ABSTRACT Virus-specific CD4 T cells are endowed with multiple functions, such as cytokine production, CD40 ligand (CD40L) expression (associated the costimulation of CD8 and B cells), degranulation cytotoxic potential). Here, we used antiviral present in human blood to evaluate relationship between production other functions cells. Antiviral specific for a virus causing persistent infection, cytomegalovirus (CMV), two viruses nonpersistent infections, influenza smallpox vaccine (vaccinia...
Here, we evaluate the cytokine coexpression profiles of human immunodeficiency virus (HIV)-specific CD4 T cells for expression cytokines gamma interferon (IFN-gamma), interleukin-2, and tumor necrosis factor alpha. In controllers, producing three or two (triple producers double producers, respectively) represented >50% total response. contrast, in noncontrollers approximately 75% responding produced only one (single producers), mostly IFN-gamma. Cells were functionally superior to those...
Here, we study the temporal expression of inhibitory receptor programmed death 1 (PD-1) on simian immunodeficiency virus (SIV) Gag-specific T cells following pathogenic SIV infection or vaccination with a DNA/modified vaccinia Ankara (DNA/MVA) vaccine and simian/human (SHIV) challenge in macaques. Following infection, majority (>95%) CD8 expressed PD-1, level PD-1 per cell increased over time. The lymph nodes rectal mucosal tissue, major sites replication, was higher compared to blood. In...
Abstract FOXP3+CD8+ T cells are present at low levels in humans; however, the function of these is not known. In this study, we demonstrate a rapid expansion CD25+FOXP3+CD8+ regulatory (Tregs) blood and multiple tissues following pathogenic SIV infection rhesus macaques. The was pronounced lymphoid colorectal mucosal tissues, preferential sites virus replication. These CD8 Tregs expressed molecules associated with immune suppressor such as CTLA-4 CD39 suppressed proliferation SIV-specific...
HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures HIV+ and HIV– individuals at different levels PD severity. This cross-sectional study included both patients with varying degrees PD. Two tooth, 2 cheek, 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB used classify sequences. R/Bioconductor (Vegan, PhyloSeq, DESeq2) was employed assess overall structure differences...
Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used live attenuated vaccine. However, correlates of protection and waning its immunity against tuberculosis poorly understood. In this study, we correlated longitudinal changes in magnitude functional quality CD4(+) CD8(+) T-cell response over a period two years after mucosal or parenteral BCG vaccination with strength mice. The vaccination-induced T cells exhibited comparable kinetics but distinct attributes in-terms...
Glycosylation is the most abundant post-translational polypeptide chain modification in nature. Although carbohydrate of protein antigens from many microbial pathogens constitutes important components B cell epitopes, role T immunity not completely understood. Here, using ELISPOT and polychromatic flow cytometry, we show that O-mannosylation adhesin, Apa, Mycobacterium tuberculosis (Mtb) crucial for its antigenicity humans mice after infection. However, subunit vaccination with both...
The influence of preexisting immunity to viral vectors is a major issue for the development viral-vectored vaccines. In this study, we investigate effect vaccinia virus on immunogenicity and efficacy DNA/modified Ankara (MVA) SIV vaccine in rhesus macaques using pathogenic intrarectal SIV251 challenge. Preexisting decreased SIV-specific CD8 CD4 T cell responses but preserved humoral immunity. addition, did not diminish control an challenge mediated by DNA/MVA vaccine. peak set point viremia...
The clinical product for a clade B HIV DNA/MVA vaccine expressing Gag, Pol, and Env has been tested immunogenicity in macaques. Responding T cells were at the threshold detection following DNA priming weeks 0 8 but underwent sharp expansions contractions MVA boosting 16 24. Both CD4 CD8 cell responses had high frequencies of cytokine coproducing with >50% memory multiple cytokines including IL-2. highest elicited to followed by then Pol. In two six macaques, also low levels neutralizing Ab...
Abstract Heterologous prime–boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses BCG-primed mice and investigated its BCG-booster potential. The response peaked 32–52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during contraction-phase of...
Abstract We tested, in rhesus macaques, the effects of a 500-fold range an admixed recombinant modified vaccinia Ankara (MVA) expressing GM-CSF (MVA/GM-CSF) on immunogenicity and protection elicited by MVA/SIV macaque 239 vaccine. High doses MVA/GM-CSF did not affect levels systemic envelope (Env)-specific Ab, but it decrease expression gut-homing receptor α4β7 plasmacytoid dendritic cells (p < 0.01) magnitudes Env-specific IgA = IgG 0.05) rectal secretions. The protective effect...
Abstract Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human vaccine. Methods. The vaccine used DNA immunogen mutated to mimic and regimen with deliveries at weeks 0 8 MVA 16 32. Twelve weekly rectal challenges 0.3 animal infectious doses SIV sootey mangabey E660 (SIVsmE660) were administered starting 6 months after...
Activated CD4 T cells are a major target of HIV infection. Results from the STEP vaccine trial highlighted potential role for total activated in promoting acquisition. However, influence insert-specific cell responses on acquisition is not known. Here, using data obtained four macaque studies, we show that DNA prime/modified vaccinia Ankara boost induced interferon γ (IFNγ+) [T helper 1 (TH1) cells] rapidly migrate to multiple tissues including colon, cervix, and vaginal mucosa. These...
Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, cells are also critical protective immunity, especially immune-compromised patients. In this study, we examined the association of cell dysfunction, as marked by expression exhaustion molecules, and posttransplant infections a cohort liver transplant We focused on Programmed Death 1 (PD-1) Ig- mucin-domain molecule 3 (Tim-3), which potent co-inhibitory receptors, their persistent often leads to...
ABSTRACT In this study, we monitored the temporal breadths, frequencies, and functions of antiviral CD4 CD8 T cells in 2 22 DNA/modified vaccinia virus Ankara-vaccinated macaques that lost control a simian-human immunodeficiency 89.6P challenge by 196 weeks postchallenge. Our results show both mutation exhaustion contributed to escape. With reappearance viremia, responding underwent an initial increase then loss breadth frequency. Antiviral gamma interferon (IFN-γ)- interleukin 2-coproducing...
Chromosomal ploidies provide a wealth of information with respect to the prognosis patients acute lymphoblastic leukemia (ALL). The is favourable in hyperdiploidy (>50 ALL), whereas pseudodiploidy and hypodiploidy have an overall poor clinical outcome. Near haploid ALL less than 30 chromosomes leukemic blasts has been reported. This extremely rare malignancy adverse course compared other leukemias. We present case near adult male diagnosis pre-B-cell ALL. presenting features relevance...
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) where pathology thought to be regulated by autoreactive T cells Th1 and Th17 phenotype. In this study we sought understand functions Presenilin 1 (PSEN1) in regulating cell effector responses experimental autoimmune encephalomyelitis (EAE) murine model MS. PSEN1 catalytic subunit γ-secretase a multimolecular protease that mediates intramembranous proteolysis. known regulate several pathways...
Advanced liver diseases (ALD) can affect immune function and compromise host defense against infections. In this study, we examined the phenotypic functional alterations in circulating monocyte dendritic cells (DCs) children with ALD undergoing transplantation (LT). Children were stratified into 2 clusters, C1 (mild) C2 (severe), on basis of laboratory parameters compared healthy pediatric controls. had a significant reduction frequencies nonclassical monocytes myeloid DCs. displayed DC...
Methods Following the initial 12 challenges, 5 uninfected rhesus were monitored for one year, boosted with 1x10 pfu of MVA/SIV239, and re-challenged 6 months later weekly rectal doses SIVE660. The resulting four macaques held an additional challenged SIV251. Avidity Env-specific IgG was determined using a NaSCN elution ELISA. Per exposure efficacy estimated leaky effects model.
Methods Three groups of rhesus macaques, eight per group, were studied. The Dryvax-naive and Dryvax-immune received the DNA/MVA SIV vaccine (DNA at weeks 0 8, rMVA 16 24). In addition, Dryvaximmune group Dryvax 1.5 years prior to DNA prime. control did not receive any vaccine. All macaques challenged intrarectally with SIV251 9 months after final MVA.