Cost-Effectiveness Analysis of Hydrus Microstent for patients with mild to moderate Primary Open-Angle Glaucoma in Canada.

Objective: Assess the cost-effectiveness of Hydrus Microstent combined with cataract surgery (CS) versus CS alone, for treating patients with mild to moderate primary open angle glaucoma (POAG).

Design: Cost-utility analysis using efficacy and safety results of a pivotal randomized clinical trial SUBJECTS: Modeled cohort of patients with mild to moderate POAG and visually significant cataract METHODS: A semi-Markov model was developed to model effects and costs over a 15-year time horizon from the Canadian public healthcare payer perspective for patients with mild or moderate POAG receiving Hydrus Microstent during CS versus CS alone. The model utilizes the HORIZON trial patient cohort.

Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP in a position elevated from the virion membrane.

Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP) are the standard of care for Ebola virus disease (EVD). Anti-GP mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP epitope that has evaded structural characterization.

Intracellular Ebola virus nucleocapsid assembly revealed by in situ cryo-electron tomography.

Filoviruses, including the Ebola and Marburg viruses, cause hemorrhagic fevers with up to 90% lethality. The viral nucleocapsid is assembled by polymerization of the nucleoprotein (NP) along the viral genome, together with the viral proteins VP24 and VP35. We employed cryo-electron tomography of cells transfected with viral proteins and infected with model Ebola virus to illuminate assembly intermediates, as well as a 9 Å map of the complete intracellular assembly.

Anti-Ebola virus mAb 3A6 with unprecedented potency protects highly viremic animals from fatal outcome and physically lifts its glycoprotein target from the virion membrane.

Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP) are the standard of care for Ebola virus disease (EVD). Anti-GP mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV . However, their neutralization mechanism is poorly understood because they target a GP epitope that has evaded structural characterization.

Cryptic-site-specific antibodies to the SARS-CoV-2 receptor binding domain can retain functional binding affinity to spike variants.

Multiple SARS-CoV-2 variants of concern have emerged and caused a significant number of infections and deaths worldwide. These variants of concern contain mutations that might significantly affect antigen-targeting by antibodies. It is therefore important to further understand how antibody binding and neutralization are affected by the mutations in SARS-CoV-2 variants.

Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology.

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection.

Outcomes and risk factors for Kahook Dual Blade excisional goniotomy with concomitant phacoemulsification: a multicentre Canadian study.

Objective: To assess the outcomes and failure risk factors for Kahook Dual Blade (KDB) excisional goniotomy with cataract surgery (phaco-KDB) in eyes with various glaucoma subtypes and severities.

Methods: This multisurgeon consecutive case series included glaucomatous eyes with cataract that underwent phaco-KDB and had a minimum follow-up of 12 months postoperatively. Efficacy was assessed by absolute and qualified surgical success (defined by different criteria) and changes in intraocular pressure (IOP) and antiglaucoma medication (AGM) at the last postoperative follow-up.

Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.

The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if acquired during pregnancy. The structure of the trimeric surface glycoprotein, essential for entry, vaccine design, and antibody neutralization, remains unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of the LCMV surface glycoprotein (GP) in its trimeric pre-fusion assembly both alone and in complex with a rationally engineered monoclonal neutralizing antibody termed 18.

Coronavirus Immunotherapeutic Consortium Database.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seen multiple anti-SARS-CoV-2 antibodies being generated globally. It is difficult, however, to assemble a useful compendium of these biological properties if they are derived from experimental measurements performed at different sites under different experimental conditions. The Coronavirus Immunotherapeutic Consortium (COVIC) circumvents these issues by experimentally testing blinded antibodies side by side for several functional activities.

Structure of the Inmazeb cocktail and resistance to Ebola virus escape.

Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike.

A cocktail of protective antibodies subverts the dense glycan shield of Lassa virus.

Developing potent therapeutics and effective vaccines are the ultimate goals in controlling infectious diseases. Lassa virus (LASV), the causative pathogen of Lassa fever (LF), infects hundreds of thousands annually, but effective antivirals or vaccines against LASV infection are still lacking. Furthermore, neutralizing antibodies against LASV are rare.

Results of the BfR MEAL Study: Highest levels of retinol found in animal livers and of β-carotene in yellow-orange and green leafy vegetables.

This Total Diet Study (TDS) provides representative data on substance levels in foods, prepared as typically consumed by the population in Germany for future dietary exposure assessment. Vitamin A is essential and must be obtained from the diet, either as preformed vitamin A or as provitamin A carotenoids. Levels of retinol and β-carotene were analysed in 333 and 271 foods, respectively.

Measles and Nipah virus assembly: Specific lipid binding drives matrix polymerization.

Measles virus, Nipah virus, and multiple other paramyxoviruses cause disease outbreaks in humans and animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly and budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of paramyxovirus M are available, and we lack the clear understanding of how viral M proteins interact with membrane lipids to mediate viral assembly and egress that is needed to guide antiviral design.

Neutralizing Antibodies against Lassa Virus Lineage I.

Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is particularly resistant to antibody neutralization. Lineage I LASV evades neutralization by half of known antibodies in the GPC-A antibody competition group and all but one of the antibodies in the GPC-B competition group.

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles.

Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination.

Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of antibody titers is urgently required. Thus, we profiled the humoral immune response in a cohort of non-human primates immunized with a recombinant SARS-CoV-2 spike glycoprotein (NVX-CoV2373) at two doses, administered as a single- or two-dose regimen.

Investigation of the Peripapillary Choriocapillaris in Normal Tension Glaucoma, Primary Open-angle Glaucoma, and Control Eyes.

Precis: The peripapillary choriocapillaris (CC) was observed to be significantly impaired in normal tension glaucoma (NTG) subjects compared with normal controls using optical coherence tomography angiography (OCTA).

Purpose: The aim was to quantitatively evaluate the peripapillary CC in NTG, primary open-angle glaucoma (POAG), and control eyes using OCTA.

Materials And Methods: Ninety eyes (30 controls, 30 NTG, and 30 POAG) from 73 patients were imaged using the Zeiss Plex Elite 9000.

A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.

Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of antibody constant domain (Fc)-mediated innate immune effector functions. Efforts to enhance Fc effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions could be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc effector profiles to help guide Fc optimization strategies.

Collaboration between the Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination.

Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™.

Collaboration between the Fab and Fc contribute to maximal protection against SARS-CoV-2 in nonhuman primates following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination.

Unlabelled: Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™.

Achieving cross-reactivity with pan-ebolavirus antibodies.

Filoviruses are the causative agents of highly lethal outbreaks in sub-Saharan Africa. Although an experimental vaccine and several therapeutics are being deployed in the Democratic Republic of Congo to combat the ongoing Ebola virus outbreak, these therapies are specific for only one filovirus species. There is currently significant interest in developing broadly reactive monoclonal antibodies (mAbs) with utility against the variety of ebolaviruses that may emerge.