A5091165851- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Streptococcal Infections and Treatments
- Neonatal and Maternal Infections
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Resistance in Staphylococcus
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- COVID-19 Clinical Research Studies
- Supramolecular Self-Assembly in Materials
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Prion Diseases and Protein Misfolding
- SARS-CoV-2 and COVID-19 Research
- Wind and Air Flow Studies
- Building Energy and Comfort Optimization
- Infant Nutrition and Health
- Bacteriophages and microbial interactions
- HIV Research and Treatment
- Immune Response and Inflammation
- Diabetes Treatment and Management
- vaccines and immunoinformatics approaches
- Refrigeration and Air Conditioning Technologies
- Click Chemistry and Applications
Epitaxial Technologies (United States)
2021-2024
Kalpavriksh
2020
Rockefeller University
2009-2012
Life and Cell Death Trying to protect animals from one form of cell death may lead by another. Two protein kinases, known as RIPK1 RIPK3 promote signaling that leads necroptosis. However, Newton et al. (p. 1357 , published online 20 February; see the Perspective Zhang Chan ) found inhibition was not always beneficial. Instead, mice expressing a with no catalytic activity died increased apoptotic death, but lacking entirely, did die perhaps because restrains apoptosis mediated caspase-8 an...
Abstract SARS-CoV-2 variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta) show increased transmissibility enhanced antibody neutralization resistance. Here we demonstrate in K18-hACE2 transgenic mice that are 100-fold more lethal than the original bearing 614D. cause severe organ lesions early strains 614D or 614G, with infection resulting distinct tissue-specific cytokine signatures, significant D-dimer depositions vital organs less pulmonary hypoxia signaling before death. However,...
Abstract Diarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the virulence factor VirG (or IcsA) clinical protection infected individuals. highly conserved among strains appealing...
Despite widespread utilization of pneumococcal conjugate vaccines (PCVs) and the resultant disease reduction, development PCVs containing additional serotypes remains a public health priority due to serotype replacement shift non-vaccine serotypes. However, incorporating existing using conventional technologies has proven problematic. Immune responses individual have consistently decreased as more polysaccharide-conjugates are added carrier suppression. Using our proprietary cell-free...
Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.e., O-polysaccharide (OPS)-based conjugates, have limited coverage—only against the immunizing serotype. Vaccines based on conserved proteins are sought for their simplicity capacity prevent disease multiple serotypes. We previously reported broad protective of VirGα, surface-exposed domain virulence factor. Seeking...
Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development vaccines to prevent transmission still needed. Pfs25, postfertilization stage parasite surface antigen, leading transmission-blocking vaccine (TBV) candidate. It...
Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus (GAS) is a public health priority. The species defining cell wall carbohydrate (GAC, Lancefield antigen) can be engineered to remove its immunodominant N-acetylglucosamine (GlcNAc) side chain, implicated in provoking autoimmune cross-reactivity rheumatic heart disease, leaving polyrhamnose core (GAC
Surface-expressed bacterial polysaccharides are important vaccine antigens but must be conjugated to a carrier protein for efficient antigen presentation and development of strong memory B cell antibody responses, especially in young children. The commonly used carriers include tetanus toxoid (TT), diphtheria (DT), its derivative CRM197, carrier-induced epitopic suppression bystander interference may limit the expanded use same pediatric immunization schedule. Recent efforts develop against...
Shigella is responsible for high burdens of diarrhea and dysentery globally. Children living in areas endemicity are the most affected, currently, there no licensed vaccines to prevent shigellosis. Vaccine approaches have traditionally targeted bacterial lipopolysaccharide as a protective antigen. O-polysaccharide (OPS) conjugated recombinant Pseudomonas aeruginosa exotoxin A (rEPA) or tetanus toxoid (TT) advanced clinical evaluation. Adequate efficacy these vaccines, particularly infant...
is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years age annually worldwide. The incidence
Nucleobindin 1 (NUCB1) is a widely expressed multidomain calcium-binding protein whose precise physiological and biochemical functions are not well understood. We engineered heterologously soluble form of NUCB1 (sNUCB1) characterized its biophysical properties. show that sNUCB1 exists as dimer in solution each monomer binds two divalent calcium cations. Calcium binding causes conformational changes judged by circular dichroism fluorescence spectroscopy experiments. Earlier reports suggested...
Periodontal diseases are chronic inflammatory of the periodontium that result in progressive destruction soft and hard tissues supporting teeth, it is most common cause tooth loss among adults. In US alone, over 100 million individuals estimated to have periodontal disease. Subgingival bacteria initiate sustain inflammation, and, although several been associated with periodontitis, Porphyromonas gingivalis has emerged as key etiological organism significantly contributing Currently,...
Shigella spp. invade the colonic epithelium and cause bacillary dysentery in humans. Individuals living areas that lack access to clean water sanitation are most affected. Even though infection can be treated with antibiotics, antimicrobial drug resistance complicates clinical management. Despite decades of effort, there no licensed vaccines prevent shigellosis. The highly conserved invasion plasmid antigens (Ipa), which components type III secretion system, participate bacterial epithelial...
Abstract Antigen-adjuvant conjugation is known to enhance antigen-specific T-cell production in vaccine models, but scalable methods are required generate site-specific for clinical translation of this technique. We report the use cell-free protein synthesis (CFPS) platform as a rapid method produce large quantities (> 100 mg/L) model antigen, ovalbumin (OVA), with incorporation p -azidomethyl- l -phenylalanine (pAMF) at two solvent-exposed sites away from immunodominant epitopes. Using...
Strain-promoted azide-alkyne cycloaddition (SPAAC) reactions like click chemistry have the potential to be highly scalable, robust, and cost-effective methods for generating small- large-molecule conjugates a variety of applications. However, despite method improvements, rates copper-based continue much faster than copper-free reactions, which makes broader deployment challenging from safety compatibility standpoint. In this study, we used zwitterionic detergent, namely, lauryldimethylamine...
Abstract SARS-CoV-2 continues to circulate globally resulting in emergence of several variants concern (VOC), including B.1.1.7 and B.1.351 that show increased transmissibility enhanced resistance antibody neutralization. In a K18-hACE2 transgenic mouse model, we demonstrate Both are 100 times more lethal than the original bearing 614D. Mice infected with exhibited severe lesions internal organs those early strains 614D or 614G. Infection also results distinct tissue-specific cytokine...
Vaccine development against group A Streptococcus (GAS) has gained traction in the last decade, fuelled by recognition of significant worldwide burden disease. Several vaccine candidates are currently being evaluated preclinical and early clinical studies. Here, we investigate two conjugate that have shown promise mouse models infection. Two antigens, J8 peptide from conserved C-terminal end M protein, carbohydrate lacking N-acetylglucosamine side chain (ΔGAC) were each conjugated to...
Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across globe. Approximately 20% pregnant women are asymptomatically colonized by GBS, which a major risk factor for severe fetal infections as well preterm birth, low birth weight, neurodevelopmental abnormalities. Current clinical interventions GBS infection limited to antibiotics, no vaccine available. We previously...
Abstract Background Due to the diversity of serotypes, exacerbated by phenomenon serotype replacement, there remains an unmet medical need for a pneumococcal conjugate vaccine (PCV) containing additional serotypes. Using cell-free protein synthesis (CFPS) platform produce enhanced carrier (eCRM®) based on CRM197 sequence, Vaxcyte is developing PCV encompassing over 30 The eCRM contains multiple insertions non-native amino acid para-azidomethyl-L-phenylalanine (pAMF) that facilitates...
Abstract Shigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years age annually worldwide. The incidence -induced diarrhea relatively low during first year life increases substantially, reaching its peak between 11 to 24 months age. This epidemiological trend hints at an early protective immunity maternal origin increase disease when maternally acquired wanes. magnitude, type, antigenic diversity,...