A5043470455- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Peptides and Activities
- Immune cells in cancer
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
- Virus-based gene therapy research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- NF-κB Signaling Pathways
- Bacillus and Francisella bacterial research
- Hepatitis B Virus Studies
- Influenza Virus Research Studies
- vaccines and immunoinformatics approaches
- Immune responses and vaccinations
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Cytomegalovirus and herpesvirus research
National Institutes of Health
2009-2023
National Cancer Institute
2014-2023
Center for Cancer Research
2013-2023
Federal Reserve
2023
Frederick National Laboratory for Cancer Research
2009-2020
National Cancer Institute
2010-2014
Frederick Community College
2012
Nanotherapeutics (United States)
2011
National Institute of Biomedical Imaging and Bioengineering
2011
Laboratory of Molecular Genetics
2011
Bacterial infection stimulates the host to mount a rapid inflammatory response. A 6-base DNA motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and 3' pyrimidines was shown contribute this response inducing polygonal B-cell activation. This stimulatory is 20 times more common in bacteria than higher vertebrates. The current work shows that same induces coordinated secretion interleukin (IL) 6, IL-12, interferon gamma (but not IL-2, IL-3, IL-4, IL-5, or IL-10) vivo...
Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines PBMC that recognize express membrane-bound human Toll-like receptor 9 (hTLR9). Cells are not responsive to become when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake (but control) into endocytic vesicles. Upon stimulation, found the same expressing stimulated by active primates but rodents, suggesting evolutionary divergence between TLR9 molecules...
Abstract Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents animal models. Their transition to clinical use requires the identification of motifs are optimally stimulatory humans. Analysis hundreds novel resulted characterization two structurally distinct “clusters” immunostimulatory ODN. One cluster (“D”) preferentially stimulates...
We previously showed that bacterial DNA contains immunostimulatory motifs consisting of unmethylated CpG dinucleotides flanked by two 5' purines and 3' pyrimidines. These rapidly trigger an innate immune response, characterized the production IL-6, IL-12, IFN-gamma. Since vaccines are constructed from plasmids DNA, we examined whether present in these contributed to immunogenicity vaccines. In vitro experiments induced same cytokines stimulated effect eliminated DNase treatment. vivo a...
Asthma is an inflammatory disease of the airways that induced by Th2 cytokines and inhibited Th1 cytokines. Despite a steady increase in incidence, morbidity, mortality from asthma, no current treatment can reduce or prevent asthma for prolonged period. We examined ability unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers cytokines, to physiological manifestations mice sensitized ragweed allergen. Administration ODN 48 h before allergen challenge increased ratio...
Abstract Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but shown limited efficacy. Nanovaccines may improve efficacy rarely clinically translated. By conjugating molecular with Evans blue (EB) into albumin-binding (AlbiVax), here we develop promising albumin/AlbiVax nanocomplexes that self-assemble vivo from AlbiVax and endogenous albumin for efficient vaccine delivery potent immunotherapy. PET pharmacoimaging, super-resolution microscopies,...
Immunostimulatory CpG oligonucleotides (ODN) activate cells that express TLR9 and have been shown to improve the host's response tumor Ags. Unfortunately, immunosuppressive microenvironment surrounds many cancers inhibits Ag-specific cellular responses thus interferes with CpG-mediated immunotherapy. Myeloid-derived suppressor (MDSC) represent an important constituent of this milieu. Large numbers MDSC are present in near sites where they inhibit activity T NK cells. Current studies indicate...
Bacterial DNA containing unmethylated CpG motifs activates mammalian lymphocytes and macrophages to produce cytokines polyclonal Ig. These include IFN-gamma, IL-12, TNF-alpha, IL-6, which are important in the control of intracellular bacterial infection. Here, we show that DNA, as well synthetic oligonucleotides motifs, induce protection against large lethal doses Francisella tularensis live vaccine strain (LVS) Listeria monocytogenes. Methylation at dinucleotides or inversion motif...
The number of B cells producing antibodies reactive with any seven autoantigens or two conventional antigens was compared at the single-cell level to total Ig-secreting present in spleens NZB, MRL lpr/lpr, and BXSB autoimmune mice. proportion lymphocytes each specificity, expressed as a percentage cell repertoire, virtually identical among congenic nonautoimmune animals. Furthermore, serum increased commensurately those autoantigens. These results indicate that systemic diseases arise from...
Abstract Mature APCs play a key role in the induction of Ag-specific immunity. This work examines whether genomic DNA released by dying cells provides stimulus for APC maturation. Double-stranded but not single-stranded triggered to up-regulate expression MHC class I/II and various costimulatory molecules. Functionally, dsDNA enhanced function vitro improved primary cellular humoral immune responses vivo. These effects were dependent on length concentration independent nucleotide sequence....
Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven activation may also have deleterious consequences, ranging from autoimmune disease to death. We find repetitive elements present at high frequency in mammalian telomeres, but rare bacteria, down-regulate CpG-induced activation. Suppressive activity correlates with the ability telomeric TTAGGG repeats form G-tetrads....
Abstract Synthetic oligodeoxynucleotides (ODN) expressing “CpG motifs” show promise as immune adjuvants, antiallergens, anticancer, and immunoprotective agents. Two structurally distinct classes of CpG ODN have been identified that stimulate human PBMC. This work establishes both types bind to are internalized by the same individual B cells, NK monocytes. However, intracellular localization “D” “K” differs, does their functional activity: type trigger monocytes cells proliferate secrete IL-6...
Peripheral blood lymphocytes (PBL) were obtained from HIV-1-infected patients at different stages of disease. The absolute number IgM-, IgG-, and IgA-producing per 10(6) PBL was increased 2.8-, 3.4-, 1.9-fold, respectively, compared with normal controls. 2-17% IgG-secreting patient cells reacted the gp160 envelope glycoprotein HIV-1 (a 737-fold increase over background), while 1-9% p24 (140-fold background). In addition to this HIV-specific B cell activation, reactive nonviral antigens such...
Abstract Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants in mice, boosting the humoral and cellular response to coadministered Ags. ODN that stimulate human PBMC are only weakly active mice. Thus, alternative animal models needed monitor activity safety of “human” vivo. This work demonstrates rhesus macaques recognize respond same trigger cells. Coadministering with heat-killed Leishmania vaccine provided significantly increased protection...
Abnormal expression of major histocompatibility complex (MHC) class I and II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability a virus injury to increase MHC gene duplicated any fragment double-stranded (ds) DNA dsRNA introduced into cytoplasm nonimmune cells. Activation sequence-independent, induced ds polynucleotides as small 25 bp length, not single-stranded polynucleotides. In...