A5071697192- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Allergic Rhinitis and Sensitization
- Cytomegalovirus and herpesvirus research
- Dermatology and Skin Diseases
- Asthma and respiratory diseases
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Cancer Research and Treatments
- Hepatitis B Virus Studies
- Cytokine Signaling Pathways and Interactions
- Hepatitis C virus research
- vaccines and immunoinformatics approaches
- Yersinia bacterium, plague, ectoparasites research
- Antimicrobial Peptides and Activities
- Viral-associated cancers and disorders
- Long-Term Effects of COVID-19
- Protein purification and stability
- Influenza Virus Research Studies
- Pharmacological Effects of Natural Compounds
- Syphilis Diagnosis and Treatment
- Neonatal Respiratory Health Research
- Food Allergy and Anaphylaxis Research
Frederick National Laboratory for Cancer Research
2018-2025
Leidos (United States)
2018-2025
Queensland Health
2023
Leidos Biomedical Research Inc. (United States)
2019
Dynavax Technologies (United States)
2000-2009
Dallas Nephrology Associates
2009
Dynavax Technologies (Germany)
2006
The Wistar Institute
1997-2000
Children's Hospital of Philadelphia
1997-1999
Philadelphia Fight
1999
Allergen specific CD4+ T cell clones generated from allergic individuals have been shown to produce increased levels of the cytokine interleukin 4 (IL-4), compared allergen nonallergic individuals. This difference between cells and with regard production in response is thought be responsible for development disease IgE synthesis atopic We examined IL-4 subjects rhinitis treated immunotherapy, a treatment which involves subcutaneous administration increasing doses highly effective beneficial...
Recent reports have identified two major classes of CpG motif-containing oligodeoxynucleotide immunostimulatory sequences (ISS): uniformly modified phosphorothioate (PS) oligodeoxyribonucleotides (ODNs), which initiate B cell functions but poorly activate dendritic cells (DCs) to make interferon (IFN)-alpha, and chimeric PS/phosphodiester (PO) ODNs containing runs six contiguous guanosines, induce very high levels plasmacytoid DC (PDC)-derived IFN-alpha stimulate cells. We generated the...
DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising tumors. Consequently, such recurrent can give rise to immunogenic peptides (FSPs) that represent ideal candidates for a vaccine against cancer. Pathogenic germline variants of cause Lynch syndrome (LS), hereditary cancer approximately...
Alveolar macrophages, resident phagocytic cells in the lung that derive from peripheral blood monocytes, are paradoxically ineffective presenting antigen to T cells. We found presentation by alveolar macrophages could be restored addition of anti-CD28 mAb cultures and indicating costimulation via CD28 pathway was defective. In addition, we activated with IFN-gamma failed express B7-1 or B7-2 antigens, which normally ligate on provide a costimulatory signal required for activation These...
Abstract Although there is good evidence that the induction of IL-4 synthesis in CD4+ T lymphocytes favored by Ag presentation B cells and not macrophages, precise molecular signals provided to enhance are clear. To examine this issue, we established an APC-independent system activate highly purified induce cytokine synthesis, using immobilized mAbs against several cell surface molecules, including CD3, CD28, CD40 ligand (CD40L). The counter-receptors for all three these molecules expressed...
IL-12 influences cytokine synthesis in unprimed CD4+ T cells by enhancing IFN-gamma and the development of Th1 cells, but its effects upon Ag-primed which are thought to have relatively fixed profiles, is less clear. We investigated capacity modify allergen-specific human lymphocytes from allergic donors after vitro stimulation. were obtained peripheral blood subjects with rhinitis, depleted activated cultured APCs allergen. dramatically inhibited IL-4 IL-10 synthesis, while it enhanced cell...
Abstract IL-15, a new cytokine primarily produced by macrophages, has been shown to exhibit several functional properties shared with IL-2. Treatment of PBMC from HIV-infected patients IL-15 resulted in an increase NK cell cytotoxicity levels similar those untreated healthy donors. This effect is independent well-characterized regulatory cytokines, as it not prevented Abs that neutralize IFNs, TNF-alpha, IL-2, or IL-12. Enhanced was accompanied significant expression cytotoxic granules....
Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A) are well described and have gained FDA approval for use in vaccines such as Cervarix. is the product chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite virtually unlimited number potential sources among strains, useable compounds within this promising class adjuvants few. We developed enzymatic combinatorial...
Abstract IL-12 activates murine and human B cells, but little information is available as to the expression function of IL-12R on lymphocytes. Here we show that latter freshly isolated from tonsils, expressed transcripts both β1 β2 chains chain mRNA was selectively increased (4- 5-fold) by incubation with Staphylococcus aureus Cowan I bacteria or IL-12. cell stimulation induced de novo two IL-18R, i.e., IL-1 receptor-related protein accessory protein-like. Functional studies showed IL-18...
Abstract IL-12 is a pivotal cytokine that links the innate and adaptive immune responses. TNF-α also plays key role in orchestrating inflammation immunity. The reciprocal influence of these two inflammatory mediators on each other may have significant impact balance shapes type extent To investigate relationship between production, we analyzed effects exposure human monocyte-derived macrophages to LPS- or Staphylococcus aureus-induced production presence absence IFN-γ. potent inhibitor p40...
As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant (APN01) will neutralize in airways, limit spread infection lung, and mitigate lung damage caused by deregulated signaling renin-angiotensin (RAS) Kinin pathways. Here, after demonstrating vitro neutralization APN01, obtaining preliminary evidence its tolerability preventive efficacy a mouse model, pursued development an formulation. prerequisite to trial,...
Immunostimulatory sequences (ISS) that contain CpG motifs have been demonstrated to exert antipathogen and antitumour immunity in animal models through several mechanisms, including the activation of natural killer (NK) cells secrete interferon-gamma (IFN-gamma) lytic activity. Since NK lack ISS receptor TLR9, exact pathway by which are activated is unclear. We determined ISS-induced IFN-gamma from primarily dependent upon IFN-alpha release plasmacytoid dendritic (PDCs), directly activates...
Abstract Lynch syndrome (LS) is a genetic disorder in which colorectal cancer caused by mutations DNA mismatch repair enzymes. Prophylactic mRNA vaccines have become the subjects of increasing interest as platforms for potential prevention such disorders. Several neoantigen sequences defective were identified expressed GEMM model Syndrome, VCMsh2, and also confirmed to be immunogenic T B cell responses background strain C57BL/6, measured IFN-g ELISPOT ELISA peptide/adjuvant-vaccinated mice....
Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is caused by monoallelic germline mutations in mismatch repair (MMR) genes (e.g., MLH1, MSH2, MSH6, and PMS2), which predispose individuals to an increased risk of developing various cancers (mainly endometrial cancer). The hallmark LS-associated tumors high microsatellite instability (MSI-H) characterized at coding mononucleotide repeats (cMNR), usually lead frameshift (FSMs) exons. These recurrent FSMs...
Abstract There are two principle subsets of dendritic cells (DCs); CD11c+CD123− myeloid DCs (MDCs) and CD11c−CD123+ plasmacytoid (PDCs). DC activation via TNF-TNFRs (e.g., CD40L) TLRs immunostimulatory oligodeoxyribonucleotides (ISS-ODNs)) is crucial for maximal stimulation innate adaptive immunity. Macaque biology being studied to improve HIV vaccines using the SIV macaque model. Using lineage (Lin) markers exclude non-DCs, Lin−HLA-DR+CD11c+CD123− MDCs Lin−HLA-DR+CD11c−CD123+ PDCs were...
CpG-C are a novel class of CpG motif-containing immunostimulatory sequences (ISS) that includes both 5'-TCG element and CpG-containing palindrome. drive all known ISS activities and, in particular, potent enhancers IFN-α from plasmacytoid dendritic cells (PDCs). In our examination sequence requirements, we determined optimal IFN-α–inducing activity could be achieved with longer palindromes. Longer palindromes also correlated maintenance the double-stranded (ds) form despite concentration pH...
Despite considerable efforts at developing therapeutic vaccines for cancer, clinical translation of preclinical successes has been challenging, largely due to the difficulty inducing strong and sustained cytotoxic T lymphocyte (CTL) responses in patients. Several peptide-based cancer have failed show sustainable tumor regression clinic, possibly because a lack optimization both adjuvant antigen components preparations. Here, we aimed develop optimize vaccine format utilizing synthetic long...