- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Brucella: diagnosis, epidemiology, treatment
- Platelet Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- Hemophilia Treatment and Research
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Blood groups and transfusion
- Blood disorders and treatments
- CAR-T cell therapy research
- Galectins and Cancer Biology
- Peptidase Inhibition and Analysis
- Protein purification and stability
- Enzyme Production and Characterization
- Insect Resistance and Genetics
- Virus-based gene therapy research
- Bacillus and Francisella bacterial research
- Heparin-Induced Thrombocytopenia and Thrombosis
Center for Biologics Evaluation and Research
2015-2024
United States Food and Drug Administration
2009-2024
Government of the United States of America
2021
University of Washington
2007
MacroGenics (United States)
2004
Hadassah Academic College
1973-1990
Food and Drug Administration
1990
University Hospital of Bern
1990
National Institutes of Health
1984
National Cancer Institute
1984
Abstract B-cell functions in antitumor immunity are not well understood. In this study, we evaluated the role of B cells development using Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 melanoma, or MCA304 sarcoma cells. To screen tumors for susceptibility to B-cell-deficient immune environments, spleen from naive C57BL/6 [wild-type (WT)] and knockout (BKO) mice were cultured with irradiated tumor vitro. When stimulated gag (but tumors), IFN-γ production CD8 T natural...
Homologous regions of five amino acids each, were identified in the NH2-terminal domain human class II beta chains and COOH terminus HIV I envelope protein. The homologous are highly conserved among different DR DQ alleles also isolates HIV. Septamers containing these sequences synthesized used for generation murine mAbs. mAbs selected this study raised against I-derived peptide reacted strongly not only with immunizing peptide, but II-derived peptide. These native MHC antigens expressed on...
We previously reported the identification of highly conserved homologous regions located in carboxy terminus HIV I gp41-envelope (aa 837-844), and amino-terminal beta chain all human HLA class II antigens 19-25). Murine monoclonal antibodies, raised against synthetic peptides from these regions, bound not only to isolated peptides, but also native gp160 molecules. In this study one-third sera I-infected individuals, at different disease stages, were found react with both gp41 II-derived...
BACKGROUND: Thrombotic events (TEs) are rare but often serious adverse that could occur after administration of immune globulin (IG) products. Our study objective was to assess occurrence recorded TEs different US‐licensed IG products and investigate potential risk factors using a large administrative database. STUDY DESIGN AND METHODS: This is retrospective claims‐based cohort individuals exposed from January 1, 2008, through September 30, 2010, HealthCore's Integrated Research Database,...
Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties carrier that enable to stimulate human B cells even in the relative absence T cells. Human immunodeficiency virus type 1 proteins conjugated B. could induce neutralizing antibodies against 1. Recently we showed characteristics lipopolysaccharide (LPS) derived from are similar those whole bacterium LPS acts T-independent mice. In this study wanted determine whether associated with...
Passive antibody prophylaxis against human immunodeficiency virus type 1 (HIV-1) has been accomplished in primates, suggesting that this strategy may prove useful humans. While specificity is crucial for neutralization, other characteristics, such as subclass, have not explored. Our objective was to compare the efficiencies of immunoglobulin G (IgG) subclasses from polyclonal HIV immune globulin (HIVIG) neutralization HIV-1 strains differing coreceptor tropism. IgG1, IgG2, and IgG3 were...
In this report we provide evidence, for the first time, that bacterial DNA in context of heat-killed Brucella abortus (HKBA) engages TLR9 dendritic cells (DC), resulting a Th1-like cytokine response. This is based on findings HKBA induction IL-12p40 is: 1) abolished DC from TLR9(-/-) mice; 2) blocked by suppressive oligodeoxynucleotides; 3) simulated derived HKBA; and 4) abrogated DNase or methylation HKBA. Furthermore, effect can be inhibited chloroquine, indicating endosomal acidification...
ABSTRACT Toll-like receptor (TLR)-expressing cells, for the first time, detected and identified a microbial contaminant in product made Escherichia coli using an old manufacturing process. It was suspected of having contaminant(s) because, although it tested negative by standard pyrogen assays, associated with adverse events early clinical trials. The assay readout is induction NF-κB and/or cytokines response to TLR activation. Four coded samples, labeled A D, including sample prepared older...
Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims-based study assessed occurrence same-day TEs HIGs during 2008-2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRD(SM) ) laboratory testing products' procoagulant Factor XIa activity by U.S. Food Drug Administration. Multivariable regression was used to estimate TE for different Of 101,956 individuals...
Abstract To study bacterial co‐infection following 1918 H1N1 influenza virus infection, mice were inoculated with the virus, followed by Streptococcus pneumoniae ( SP ) 72 h later. Co‐infected exhibited markedly more severe disease, shortened survival time and lung pathology, including widespread thrombi. Transcriptional profiling revealed activation of coagulation only in co‐infected mice, consistent extensive thrombogenesis observed. Immunohistochemistry showed expression tissue factor F3...
Hyperimmune immunoglobulin (hCoV-2IG) generated from SARS-CoV-2 convalescent plasma (CP) are under evaluation in clinical trials. Here we explored the antibody epitope repertoire, and virus neutralizing capacity of six hCoV-2IG batches as well nine CP against emerging variants concern (VOCs). Epitope-mapping by gene-fragment phage display library spanning spike demonstrated broad recognition multiple antigenic sites entire that was higher for than CP, with predominant binding to fusion...
Abstract Cattle and humans are susceptible to infection with the Gram-negative intracellular bacterium Brucella abortus. Heat-killed B. abortus (HKBA) is a strong Th1 adjuvant carrier. Previously, we have demonstrated that dendritic cells produce IL-12 in response HKBA stimulation. In present study, use knockout mice vitro reconstitution assays examine contribution of signaling by Toll-like receptors (TLRs) their immediate downstream initiator, myeloid differentiation protein MyD88,...
ABSTRACT The most common infections in primary immune deficiency disease (PIDD) patients involve encapsulated bacteria, mainly Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus). Thus, it is important to know the titers of Hib- pneumococcus-specific antibodies that are present globulin (Ig) intravenous (IGIV) preparations used treat PIDD. In this study, seven IGIV were tested by enzyme-linked immunosorbent assay opsonophagocytic activity for antibody capsular...
Defining the pattern of lymphokine production associated with Brucella abortus is critical for advancing development B. as a vaccine carrier. In present study we investigated ability heat-inactivated or lipopolysaccharide from to induce purified human T cells in vitro. Gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 induction was assayed by mRNA-specific PCR enzyme-linked immunosorbent assay bioassay protein production. Following depletion monocytes B cells, increased...
Therapeutic proteins are derived from complex expression/production systems, which can result in minor conformational changes due to preferential codon usage different organisms, post-translational modifications, etc. Subtle differences often undetectable by bioanalytical methods but sometimes profoundly impact the safety, efficacy and stability of products. Numerous exist characterize primary structure proteins, post translational modifications; protein-substrate/protein/protein...
Viral infections are often accompanied by pulmonary microvascular leakage and vascular endothelial dysfunction via mechanisms that not completely defined. Here, we investigated the effect of Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog viral double-stranded RNA (dsRNA) commonly used to simulate infections, on barrier function tight junction integrity primary human lung cells. Poly(I:C) stimulated IL-6, IL-8, TNFα, IFNβ production in...
Development of a vaccine which is capable generating strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be inducing secretion interleukin-12 (IL-12), pivotal factor for differentiation Th1 or Tc1 cells. We have previously shown heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma by T In present study, we demonstrate B. lipopolysaccharide (LPS) from IL-12 p40 mRNA...