A5031605661- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- Congenital Diaphragmatic Hernia Studies
- SARS-CoV-2 detection and testing
- Genomics and Phylogenetic Studies
- Neonatal Respiratory Health Research
- Pneumonia and Respiratory Infections
- Cancer Research and Treatments
- vaccines and immunoinformatics approaches
- Biosimilars and Bioanalytical Methods
- Inhalation and Respiratory Drug Delivery
AstraZeneca (United States)
2022-2025
Meso Scale Discovery (United States)
2020
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2014-2016
National Institutes of Health
2014-2016
Purdue University West Lafayette
2009-2011
State Street (United States)
2009-2010
Abstract Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of respiratory syncytial virus (RSV) F protein, which has been studied in preterm and full-term infants phase 2b 3 MELODY trials. We analyzed serum samples collected from 2,143 during these studies to characterize baseline levels RSV-specific immunoglobulin G antibodies neutralizing (NAbs), duration RSV NAb following nirsevimab administration, risk exposure first year life infant’s...
Many flaviviruses are significant human pathogens, with the humoral immune response playing an essential role in restricting infection and disease. CR4354, a monoclonal antibody isolated from patient, neutralizes West Nile virus (WNV) at postattachment stage viral life-cycle. Here, we determined structure of WNV complexed Fab fragments CR4354 using cryoelectron microscopy. The outer glycoprotein shell mature particle is formed by 30 rafts three homodimers surface protein E. binds to...
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from infections were subtyped, sequenced analyzed for binding site substitutions; subsequently, recombinant RSVs engineered microneutralization susceptibility testing. Here we show frequency caused...
Therapeutic anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (MAbs) provide immunosuppressed and vulnerable populations with prophylactic treatment interventions against disease 2019 (COVID-19). AZD7442 (tixagevimab-cilgavimab) is a combination of extended-half-life neutralizing MAbs that bind to distinct epitopes on the receptor binding domain (RBD) SARS-CoV-2 spike protein. The Omicron variant concern carries mutations at >35 positions in protein has...
Abstract Background AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab). Methods This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated administered intramuscularly (300 mg) or intravenously (300, 1000, 3000 in healthy adults (aged 18–55 years). The primary end point was safety tolerability. Secondary points...
Robust, quantitative serology assays are required to accurately measure antibody levels following vaccination and natural infection. We present validation of a quantitative, multiplex, SARS-CoV-2, electrochemiluminescent (ECL) assay; show correlation with two established SARS-CoV-2 immunoassays; calibration results for reference standards.Precision, dilutional linearity, ruggedness, analytical sensitivity specificity were evaluated. Clinical assessed using serum from prepandemic polymerase...
Background Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in disease 2019 (COVID-19) vaccinees typically produces milder than unvaccinated individuals. Methods To explore attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination...
The nasal mucosa is an important initial site of host defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, intramuscularly administered vaccines typically do not achieve high antibody titers in the mucosa. We measure anti-SARS-CoV-2 spike immunoglobulin G (IgG) and IgA epithelial lining fluid (NELF) following intramuscular vaccination 3,058 participants from immunogenicity substudy a phase 3, double-blind, placebo-controlled study AZD1222...
Abstract Background Prior studies of the SARS-CoV-2 monoclonal antibody (mAb) combination AZD7442 (tixagevimab/cilgavimab) included limited numbers immunocompromised (IC) participants, target population for COVID-19 pre-exposure prophylaxis. We report repeat dosing data in an IC population. Methods The randomized, open-label, ENDURE study (NCT05375760) enrolled individuals aged ≥ 18 yrs, weighing 40 kg, moderately to severely or at risk inadequate vaccine response, and SARS-CoV-2–negative...
The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as procapsid ~4,000 protein subunits of 11 different kinds. undergoes major changes in structure and composition it matures, process driven by proteolysis expulsion the internal scaffolding protein. Assembly also relies on an external protein, triplex, α2β heterotrimer that coordinates neighboring capsomers becomes stabilizing clamp mature...
This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar AZD1222 (ChAdOx1 nCoV-19), and as third-dose boosters.
Background Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now widespread; however, the degree of cross-immunity between SARS-CoV-2 and endemic, seasonal human coronaviruses (HCoVs) remains unclear. Methods HCoV was evaluated in adult participants enrolled a US sub-study phase III, randomized controlled trial (NCT04516746) AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination for one-year. Anti-HCoV spike-binding antibodies against HCoV-229E, HCoV-HKU1, HCoV-OC43,...
Abstract Objectives The evolution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard measuring virus‐neutralising (nAb) titres in serum. However, authentic virus‐based pose inherent practical challenges nAb SARS‐CoV‐2 variants (e.g. storing infectious viruses and testing at biosafety level‐3 facilities)....
The urgency and importance of organizing a global effort to harmonize clinical assay validation specific the vaccine industry was identified during drafting 2020 White Paper in Bioanalysis due lack clarity regulatory guidance/guidelines immunoassay validation. Indeed, Workshop on Recent Issues (WRIB) issues yearly, which is one high-profile articles Journal focused detailed discussions recommendations Since 2017, participation WRIB working groups by experts regulators has rapidly increased...
The herpes simplex virus 1 (HSV-1) capsid is a huge assembly, ∼1,250 Å in diameter, and composed of thousands protein subunits with combined mass ∼200 MDa, housing 100-MDa genome. First, procapsid formed through coassembly the surface shell an inner scaffolding shell; then matures via major structural transformation, triggered by limited proteolysis proteins. Three mature capsids are found nuclei infected cells. A empty, B retain shrunken shell, C capsids-which develop into infectious...
Nirsevimab is an extended half-life, highly potent neutralizing monoclonal antibody against the respiratory syncytial virus (RSV) fusion protein, with efficacy in preventing RSV-associated medically attended (MA) lower tract infection (LRTI) infants and vulnerable children (aged ≤24 months). This post-hoc exploratory analysis examined incidence of LRTI from RSV other pathogens during a 2:1 randomized, double-blind, placebo-controlled, phase 3 study nirsevimab, healthy-term late-preterm (i.e....