A5102969456- Malaria Research and Control
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Vector-borne infectious diseases
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Neuroscience and Neuropharmacology Research
- Protein purification and stability
- Nerve injury and regeneration
- Vector-Borne Animal Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- vaccines and immunoinformatics approaches
- RNA regulation and disease
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Toxin Mechanisms and Immunotoxins
- T-cell and B-cell Immunology
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Cardiac, Anesthesia and Surgical Outcomes
- Influenza Virus Research Studies
- Peroxisome Proliferator-Activated Receptors
- Parasitic Infections and Diagnostics
- Cardiovascular Health and Disease Prevention
National Institute of Allergy and Infectious Diseases
2010-2023
National Institutes of Health
2010-2023
Sichuan Agricultural University
2020
Vector Oncology (United States)
2014
Christiana Care Health System
2011-2012
Johns Hopkins University
2010
Johns Hopkins Bayview Medical Center
2010
Mitchell Institute
2008
Texas A&M University
1996-2008
Walter Reed Army Institute of Research
2007
Background Pfs25 and Pvs25, surface proteins of mosquito stage the malaria parasites P. falciparum vivax, respectively, are leading candidates for vaccines preventing transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed safety immunogenicity recombinant Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. Methodology/Principal Findings The trial was conducted at Johns Hopkins Center Immunization Research, Washington DC, USA, between...
Niacin is a widely used lipid-regulating agent in dyslipidemic patients. Previously, we have shown that niacin inhibits triacylglycerol synthesis. In this report, using HepG2 cells, examined the effect of on mRNA expression and microsomal activity diacylglycerol acyltransferase 1 2 (DGAT1 DGAT2), last committed but distinctly different enzymes for triglyceride Addition to DGAT assay reaction mixture dose-dependently (0-3 mM) inhibited by 35-50%, IC(50) was found be 0.1 mM. Enzyme kinetic...
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated improvement its functional immunogenicity after conjugation to EPA, recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results open-label, dose-escalating Phase 1 trial assess the safety Pfs25-EPA conjugates...
BACKGROUND. Vaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication, and clinical trials have targeted zygote antigen Pfs25 decades. We reported a protein-protein conjugate vaccine formulated in alum adjuvant induced serum functional activity both US Malian adults. However, antibody levels declined rapidly, transmission-reducing required 4 doses. Functional immunogenicity durability must be improved before advancing transmission-blocking vaccines...
The role of a nuclear factor κB (NF‐κB) in NMDA receptor‐mediated neuroprotection is not known. A candidate sequence from the 5′ flanking region exon 3 rat brain‐derived neurotrophic (BDNF) gene was used to show that exposure cerebellar granule cells 100 μ m activated specific DNA binding activity blocked by receptor antagonist MK‐801. Anti‐p65 antibody or anti‐p50 ‘supershifted’ activity, suggesting DNA–protein complex composed p65 and p50 subunits. when neurons were transfected with...
Protective immunity against the ehrlichial pathogen Anaplasma marginale has been hypothesized to require induction of immunoglobulin G2 (IgG2) antibody outer membrane protein epitopes and coordinated activation macrophages for phagocytosis killing. In present study, cell-mediated immune responses, including IgG isotype switching, were characterized in calves immunized with purified membranes Florida strain A. marginale. Importantly, these subsequently shown be protected upon experimental...
Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is leading blood-stage malaria vaccine candidate. This the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with novel adjuvant CPG 7909.A phase trial was conducted at University Rochester 75 malaria-naive volunteers to assess safety and immunogenicity AMA1-C1/Alhydrogel+CPG 7909 vaccine. Participants were sequentially enrolled randomized within dose escalating cohorts receive three...
Background Inhibition of parasite growth is a major objective blood-stage malaria vaccines. The in vitro assay inhibitory activity (GIA) widely used as surrogate marker for vaccine efficacy the down-selection candidate Here we report first study to examine relationship between vivo Plasmodium falciparum rates and GIA humans experimentally infected with malaria. Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised AMA1/C1-Alhydrogel+CPG...
Abstract The Plasmodium falciparum protein, apical membrane antigen 1 forms a complex with another parasite rhoptry neck protein 2, to initiate junction formation the erythrocyte and is essential for merozoite invasion during blood stage of infection. Consequently, has been target vaccine development but vaccination alone in controlled human malaria infections failed protect showed limited efficacy field trials. Here we show that AMA1–RON2L Freund’s adjuvant protects Aotus monkeys against...
Merozoite surface protein 1(42) (MSP1(42)) is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42) were mixed (MSP1(42)-C1). To improve level antibody response, MSP1(42)-C1 was formulated with Alhydrogel plus novel adjuvant CPG 7909.A Phase 1 clinical trial conducted in healthy malaria-naïve adults at Center for Immunization Research Washington, D.C., evaluate safety...
The development of effective vaccines against difficult disease targets will require the identification new subunit vaccination strategies that can induce and maintain immune responses in humans. Here we report on a phase 1a clinical trial using AMA1 antigen from blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant without CPG 7909, or vectored vaccines—chimpanzee adenovirus ChAd63 orthopoxvirus MVA. A variety...
The signal transduction and molecular mechanisms underlying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-mediated neuroprotection are unknown. In the present study, we determined a major AMPA receptor-mediated neuroprotective pathway. Exposure of cerebellar granule cells to (500 microM) + aniracetam (1 microM), known blocker receptor desensitization, evoked an accumulation brain-derived neurotropic factor (BDNF) in culture medium enhanced TrkB-tyrosine phosphorylation...
A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of blood stage vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination FVO 3D7 alleles recombinant AMA1 MSP1(42), with equal amounts by weight each four proteins mixed, bound Alhydrogel®, administered adjuvant Thirty (30) volunteers were enrolled two groups, 15 receiving up three doses 40 µg total protein at Days 0, 56, 180, 160 on same schedule. Most related...
ABSTRACT Major surface proteins of Anaplasma marginale are vaccine candidates. We recently demonstrated that immunization calves with outer membranes the Florida strain A. resulted in protective immunity correlated a memory CD4 + T-lymphocyte response specific for major protein 1 (MSP-1), MSP-2, and MSP-3 (W. C. Brown, V. Shkap, D. Zhu, T. McGuire, W. Tuo, F. McElwain, G. H. Palmer, Infect. Immun. 66:5406–5413, 1998). As immunogens, these have been shown to induce complete or partial...
N-Methyl-D-aspartate (NMDA) at a subtoxic concentration (100 microM) promotes neuronal survival against glutamate-mediated excitotoxicity via brain-derived neurotrophic factor (BDNF) autocrine loop in cultured cerebellar granule cells. The signal transduction mechanism(s) underlying NMDA neuroprotection, however, remains elusive. mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 (PI3-K) pathways alter gene expression are involved synaptic plasticity survival. This study...
Abstract Genogroup II ehrlichia, including the agent of human granulocytic ehrlichiosis, Ehrlichia phagocytophila, and bovine pathogen Anaplasma marginale, express a markedly immunodominant outer membrane protein designated major surface 2 (MSP2). MSP2 is encoded by multigene family, resulting in expression variant B cell epitopes. variants are sequentially expressed repeated cycles rickettsemia that characterize persistent A. marginale infection control each rickettsemic cycle associated...