A5034058121- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Bacillus and Francisella bacterial research
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Microbial Inactivation Methods
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Bacterial Genetics and Biotechnology
- Disaster Response and Management
- Yersinia bacterium, plague, ectoparasites research
- Insect and Pesticide Research
- Carbohydrate Chemistry and Synthesis
- COVID-19 epidemiological studies
- Carcinogens and Genotoxicity Assessment
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Phagocytosis and Immune Regulation
- Virology and Viral Diseases
- Corporate Identity and Reputation
- Genomics and Phylogenetic Studies
- Vector-borne infectious diseases
- Biochemical and Structural Characterization
The University of Texas Medical Branch at Galveston
2006-2024
Louisiana State University
2024
Battelle
2012-2023
Environmental Protection Agency
2017
The University of Texas MD Anderson Cancer Center
2015
National Institute of Allergy and Infectious Diseases
2008
National Institutes of Health
2008
John Sealy Hospital
2007
Duquesne University
2002-2005
University of Pittsburgh
2000
Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from convalescent patient. Antibody-mediated neutralization occurs via an epitope within receptor-binding domain Spike protein. SC31 exhibited anti-SARS-CoV-2 activities in multiple animal models. In infected K18-human ACE2...
Abstract Purpose CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor was safely administered to metastatic patients in combination with paclitaxel (P) and appeared reduce CSC window-of-opportunity trial operable cancer. The fRida (NCT02370238) evaluated addition R weekly first-line therapy (m) TNBC. Subjects Methods untreated mTNBC were randomized 1:1 or placebo days 1–21 P 80...
Chikungunya virus (CHIKV) infection can result in chikungunya fever (CHIKF), a self-limited acute febrile illness that progress to chronic arthralgic sequelae large percentage of patients. A new measles virus-vectored vaccine was developed prevent CHIKF, and we tested it for immunogenicity efficacy nonhuman primate model.Nine cynomolgus macaques were immunized boosted with the or sham-vaccinated. Sera taken at multiple times during vaccination phase assess antibody responses against CHIKV....
The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection. However, pathogenesis ARDS SRAS-CoV-2 infection remains largely unknown. In present study, we examined apoptosis postmortem lung sections from COVID-19 patients and tissues a non-human primate model infection, cell-type manner, including type 1 2 alveolar cells vascular endothelial (ECs), macrophages, T cells. Multiple-target...
The causative agent of anthrax, Bacillus anthracis, produces two toxins that contribute in part to its virulence. Lethal toxin is a metalloprotease cleaves upstream mitogen-activated protein kinase kinases. Edema calmodulin-dependent adenylate cyclase. Previous studies demonstrated the anthrax are important immunomodulators promote immune evasion bacterium by suppressing activation macrophages and dendritic cells. Here we showed injection sublethal doses either lethal or edema into mice...
ABSTRACT Prevention of inhalation anthrax requires early and extended antibiotic therapy, therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, rabbits against anthrax. Control animals challenged with Bacillus anthracis Ames spores by the intranasal route died within 3 7 days. AVP-21D9 alone provided minimal protection in murine model, but its efficacy was notably...
Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that used clinically as an antiviral outside the United States. A machine-learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone potent in vitro EBOV inhibitor, making it candidate for treatment of Ebola disease (EVD). In present study, series ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated has excellent solubility, high Caco-2...
Recent outbreaks of the Ebola virus (EBOV) have focused attention on dire need for antivirals to treat these patients. We identified pyronaridine tetraphosphate as a potential candidate it is an approved drug in European Union which currently used combination with artesunate treatment malaria (EC50 between 420 nM-1.14 μM against EBOV HeLa cells). Range-finding studies mice directed us single 75 mg/kg i.p. dose 1 hr after infection resulted 100% survival and statistically significantly...
Background: Persistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, conceived in 2020, that evoke protective spike antibody responses are being deployed mass public health vaccination programs. Recent data suggests, however, as sequence variation the genome accumulates, some vaccines may lose efficacy. Methods: Using macaque model SARS-CoV-2 infection, we tested efficacy peptide-based vaccine targeting...
Transmission of Ebola virus (EBOV) primarily occurs via contact exposure mucosal surfaces with infected body fluids. Historically, nonhuman primate (NHP) challenge studies have employed intramuscular (i.m.) or small particle aerosol exposure, which are largely lethal routes infection, but mimic worst-case scenarios such as a needlestick intentional release, respectively. When exposed by more likely natural limited NHP shown delayed onset disease and reduced mortality. Here, we performed...
ABSTRACT A delayed inflammatory response is a prominent feature of infection with Yersinia pestis , the agent bubonic and pneumonic plague. Using rat model plague, we examined lymph node histopathology, transcriptome, extracellular cytokine levels to broadly characterize kinetics extent host Y. how it influenced by virulence plasmid (pYV). Remarkably, dissemination multiplication wild-type during stage disease did not induce any detectable gene expression or cells in developing bubo. Only...
The mosquito midgut ookinete stage of the malaria parasite, Plasmodium, possesses microneme secretory organelles that mediate locomotion and wall egress to establish sporogonic stages subsequent transmission. purpose this study was 2-fold: 1) determine whether there exists a single micronemal population with respect soluble membrane-associated secreted proteins; 2) evaluate proteins chitinase (PgCHT1), circumsporozoite TRAP-related protein (CTRP), von Willebrand factor A domain-related...
Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection Ames spores, regardless inoculation method. Further, all but one animals (23/24) resistant rechallenge spores by respiratory method 5 weeks after primary challenge....
Bacillus anthracis toxins can be neutralized by antibodies against protective antigen (PA), a component of anthrax toxins. Anthrivig (human immunoglobulin), also known as AIGIV, derived from plasma humans immunized with BioThrax (anthrax vaccine adsorbed), is under development for the treatment toxemia following exposure to spores. The pharmacokinetics (PK) AIGIV was assessed in naive animals and healthy human volunteers, efficacy exposed via inhalation aerosolized B. In clinical study,...
Quinacrine hydrochloride is a small-molecule, orally bioavailable drug that has been used clinically as an antimalarial and for many other applications. A machine learning model trained on Ebola virus (EBOV) screening data identified quinacrine potent (nanomolar) in vitro inhibitor.
ABSTRACT Previous work (P. Castric, F. J. Cassels, and R. W. Carlson, Biol. Chem. 276:26479-26485, 2001) has shown the Pseudomonas aeruginosa 1244 pilin glycan to be covalently bound a serine residue. N-terminal sequencing of fragments produced from endopeptidase treatment identified by reaction with glycan-specific monoclonal antibody indicated that was present between residue 75 carboxy terminus. Further these peptides revealed residues 75, 81, 84, 105, 106, 108 were not modified....
ABSTRACT Appropriate animal models are required to test medical countermeasures bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing according the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded each NHP exposed lethal dose of Bacillus anthracis Ames spores. Specific diagnostic parameters were detected relatively early disease progression, i.e., by blood culture (∼37 h...
Background We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and effective window treatment to assess added benefit provided by over standard antibiotic alone a New Zealand white rabbit model inhalational anthrax. Methods Rabbits were exposed lethal dose aerosolized spores Bacillus anthracis (Ames strain) treated intravenously either placebo, (normal immune globulin intravenous, IGIV) or 15 U/kg AIGIV, along oral at various time points (30–96...
Abstract SARS-CoV-2-neutralizing antibodies are promising therapeutics for COVID-19. However, little is known about the mechanisms of action these or their effective dosing windows. We report discovery and development SC31, a potent SARS-CoV-2 neutralizing IgG1 antibody, originally isolated from convalescent patient at day 27 after onset symptoms. Neutralization occurs via binding epitope that maps within ACE2 interface Spike protein, conserved across all common circulating mutants. In...
Molnupiravir (EIDD-2801) is a prodrug of ribonucleoside analogue that currently being used under US FDA emergency use authorization for the treatment mild to moderate COVID-19. We evaluated molnupiravir efficacy as an oral in rhesus macaque model SARS-CoV-2 infection. Twenty non-human primates (NHPs) were challenged with and treated 75 mg/kg (n = 8) or 250 twice daily by gavage 7 days. The NHPs observed 14 days post-challenge monitored clinical signs disease. After challenge, all groups...
Lymphocytic choriomeningitis virus (LCMV) and Lassa (LASV) share many genetic biological features including subtle differences between pathogenic apathogenic strains. Despite remarkable similarity, the viscerotropic WE strain of LCMV causes a fatal LASV fever-like hepatitis in non-human primates (NHPs) while mouse-adapted Armstrong (ARM) is deeply attenuated NHPs can vaccinate against LCMV-WE challenge. Here, we demonstrate that internalization more sensitive to depletion membrane...
ABSTRACT The development of an appropriate animal therapeutic model is essential to assess the potential efficacy therapeutics for use in event a Bacillus anthracis exposure. We conducted natural history study that showed New Zealand White rabbits exhibited significant increase body temperature (SIBT), changes hematologic parameters, and increases C-reactive protein succumbed disease with average time death approximately 73 h following aerosol challenge B. Ames spores. SIBT was used as...