Exequiel Dellota
A5073637458- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Complement system in diseases
- Viral Infections and Immunology Research
- Virus-based gene therapy research
- Long-Term Effects of COVID-19
- COVID-19 epidemiological studies
- Plant-Microbe Interactions and Immunity
- SARS-CoV-2 detection and testing
- Plant Virus Research Studies
- vaccines and immunoinformatics approaches
- Plant Disease Resistance and Genetics
- Lipid Membrane Structure and Behavior
- Bacillus and Francisella bacterial research
- Monoclonal and Polyclonal Antibodies Research
VIR Biotechnology (United States)
2021-2024
University of California, Riverside
2017
An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape
ABSTRACT Sotrovimab (VIR-7831) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). were derived from a parent antibody (S309) isolated memory B cells 2003 (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in Fc region to prolong serum half-life. In addition, encodes GAALIE that has been shown previously evoke CD8+ T-cells context vivo viral infection. neutralize wild-type variant...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 BA.4 BA.5 increasing in prevalence worldwide. We show that large number sublineage spike mutations leads to enhanced angiotensin-converting enzyme (ACE2) binding, reduced fusogenicity, dampening plasma neutralizing activity elicited by infection or seven clinical vaccines relative ancestral virus....
Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding...
Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots 1 . Their impact on viral infection, transmission, and efficacy of vaccines therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. XBB.1 bind ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures the BQ.1.1 RBDs bound to human S309 Fab (sotrovimab parent) explain altered recognition...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing sufficiently potent clinical development and retain activity despite remain elusive. We identified human mAb, designated VIR-7229, which targets the receptor-binding motif (RBM) with unprecedented cross-reactivity all sarbecovirus clades,...
Patients on dialysis are at risk of severe course SARS-CoV-2 infection. Understanding the neutralizing activity and coverage variants vaccine-elicited antibodies is required to guide prophylactic therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis 13 peritoneal patients after two doses BNT162b2 or mRNA-1273 vaccines, we found that 35% had low-level undetectable IgG Spike (S). Neutralizing against vaccine-matched Delta variant were...
Abstract Investigating the mechanisms of SARS-CoV-2 cellular infection is key to better understand COVID-19 immunity and pathogenesis. Infection, which involves both cell attachment membrane fusion, relies on ACE2 receptor that paradoxically found at low levels in respiratory tract, suggesting additional facilitating may exist. Here we show C-type lectin receptors, DC-SIGN, L-SIGN sialic acid-binding Ig-like 1 (SIGLEC1) function as auxiliary receptors by enhancing ACE2-mediated modulating...
The recent emergence of SARS-CoV-2 variants concern (VOC) and the recurrent spillovers coronaviruses in human population highlight need for broadly neutralizing antibodies that are not affected by ongoing antigenic drift can prevent or treat future zoonotic infections. Here, we describe a monoclonal antibody (mAb), designated S2X259, recognizing highly conserved cryptic receptor-binding domain (RBD) epitope cross-reacting with spikes from all sarbecovirus clades. S2X259 neutralizes...
Abstract An ideal anti-SARS-CoV-2 antibody would resist viral escape 1–3 , have activity against diverse SARS-related coronaviruses 4–7 and be highly protective through neutralization 8–11 effector functions 12,13 . Understanding how these properties relate to each other vary across epitopes aid development of therapeutics guide vaccine design. Here, we comprehensively characterize escape, breadth, potency a panel SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including...
An ideal anti-SARS-CoV-2 antibody would resist viral escape 1-3 , have activity against diverse SARS-related coronaviruses 4-7 and be highly protective through neutralization 8-11 effector functions 12,13 . Understanding how these properties relate to each other vary across epitopes aid development of therapeutics guide vaccine design. Here, we comprehensively characterize escape, breadth, potency a panel SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S309 4...
Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity, and cross-reactivity of serum antibodies MBCs in 155 SARS-CoV-2 infected vaccinated individuals over 16-month time frame. SARS-CoV-2-specific reached steady-state titers comparable kinetics individuals. Whereas targeted both prefusion postfusion Spike (S), most vaccine-elicited were specific for S, consistent use prefusion-stabilized S mRNA vaccines....
Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies MBCs in 155 SARS-CoV-2 infected vaccinated individuals over 16-month timeframe. SARS-CoV-2-specific reached steady-state titers comparable kinetics individuals. Whereas targeted both pre- postfusion Spike (S), most vaccine-elicited were specific for prefusion S, consistent use prefusion-stabilized S mRNA...
Abstract Patients on dialysis are at risk of severe course SARS-CoV-2 infection. Understanding the neutralizing activity and coverage variants vaccine-elicited antibodies is required to guide prophylactic therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis 13 peritoneal patients after two doses BNT162b2 or mRNA-1273 vaccines, we found that 35% had low-level undetectable IgG Spike (S). Neutralizing against vaccine-matched Delta...