A5064589798- Viral gastroenteritis research and epidemiology
- Clostridium difficile and Clostridium perfringens research
- Bacteriophages and microbial interactions
- Protein purification and stability
- Microscopic Colitis
- RNA Interference and Gene Delivery
- Biosensors and Analytical Detection
- Cytomegalovirus and herpesvirus research
- Microfluidic and Bio-sensing Technologies
- Antimicrobial Resistance in Staphylococcus
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Microbial infections and disease research
- Hepatitis B Virus Studies
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Vibrio bacteria research studies
United States Military Academy
2014-2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2015-2023
Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors bacterium large clostridial toxins (LCTs), TcdA and TcdB, which largely responsible for symptoms disease. Recent outbreaks CDI have been associated with emergence hypervirulent strains, such as NAP1/BI/027, many strains also produce third toxin, binary toxin (CDTa CDTb). These increased morbidity higher mortality. Here we present pre-clinical data describing...
Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates common. One reason for this that hypervirulent C. strains often have a binary toxin termed the toxin, in addition to enterotoxins TsdA TsdB. The has an enzymatic component, CDTa, pore-forming or delivery subunit CDTb. CDTb was characterized here using combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, other biophysical methods. In absence...
Abstract There is growing interest in the development of new vaccines based on live‐attenuated viruses (LAVs) and virus‐like particles. The large size these vaccines, typically 100–400 nm, significantly complicates use sterile filtration. objectives this study are to examine performance several commercial filters for filtration a cytomegalovirus vaccine candidate (referred as LAV) develop evaluate model nanoparticle suspension perform more quantitative assessment. Data obtained with mixture...
The toxicity of Clostridium difficile large clostridial toxin B (TcdB) can be reduced by many orders magnitude a combination targeted point mutations. However, TcdB mutant with five mutations (referred to herein as mTcdB) still has residual that detected in cell-based assays and in-vivo mouse assays. This effectively removed treatment formaldehyde solution. Storage the formaldehyde-treated mTcdB liquid result reversion over time back level toxicity, rate dependent on storage temperature. We...
Abstract Live virus vaccine (LVV) purification, employing chromatography, can be challenged by low binding capacities and elution yields. Alternatively, processes relying solely on enzymatic digestion steps size‐based membrane separations limited suboptimal reduction of process related impurities poorly scalable unit operations. Here, we demonstrate that the combination flowthrough mode chromatography an ultrafiltration/diafiltration (UF/DF) operation delivers a purification for two...
Nanoparticle hydrophobicity is a key factor controlling the stability, adhesion, and transport of nanoparticle suspensions. Although number approaches have been presented for evaluating hydrophobicity, these methods are difficult to apply larger nanoparticles viruses (>100 nm in size) that increasing importance drug delivery gene therapy. This study investigated use new analytical hydrophobic interaction chromatography method employing 5.0 μm pore size polyvinylidene fluoride membrane as...
Human cytomegalovirus (HCMV) is currently a major cause of congenital disease in newborns and organ failure transplant recipients. Despite decades efforts, an effective vaccine against HCMV has yet to be developed. However, the discovery pentameric gH complex on viral surface which contains potent neutralizing epitopes may help enable development vaccine. In our company ongoing Phase II clinical trial whole-live virus (V160), been restored live attenuated AD169 strain. The reconstructed...
Continuous multi-column chromatography (CMCC) has been successfully implemented to address biopharmaceutical biomolecule instability, improve process efficiency, and reduce facility footprint capital cost. This paper explores the implementation of a 4-membrane mode continuous multi-membrane (CMMC) for large viral particle in just few weeks. CMMC improves efficiency step by enabling higher loads with smaller membranes multiple cycles column use steady-state bioprocessing. The separation...
Abstract Targeting Clostridium difficile infection (CDI) is challenging because treatment options are limited, and high recurrence rates common. One reason for this that hypervirulent CDI often has a binary toxin termed the C. (CDT), in addition to enterotoxins TsdA TsdB. CDT an enzymatic component, CDTa, pore-forming or delivery subunit CDTb. CDTb was characterized here using combination of single particle cryoEM, X-ray crystallography, NMR, other biophysical methods. In absence two novel...