Nicole Sprugasci
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Viral Infections and Immunology Research
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- COVID-19 epidemiological studies
- CAR-T cell therapy research
- Hepatitis C virus research
- Long-Term Effects of COVID-19
- Hepatitis B Virus Studies
VIR Biotechnology (United States)
2022-2025
Vir Biotechnology (Switzerland)
2020-2022
Scuola Cantonale di Commercio Bellinzona
2022
Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as 13 September 2020. We report isolation and characterization two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 S2M11) protect hamsters against challenge. Cryo-electron microscopy structures show S2E12 S2M11 competitively block angiotensin-converting enzyme (ACE2) attachment also locks spike in a closed...
An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape
Targeting a range of betacoranaviruses In the past 20 years, three highly pathogenic β-coronaviruses have crossed from animals to humans, including most recent: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A spike protein that decorates these viruses has an S1 domain binds host cell receptors and S2 fuses viral membranes allow entry. The is target many neutralizing antibodies but more genetically variable than S2, can exert selective pressure, leading resistant variants....
The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind all human-infecting proteins from severe acute respiratory syndrome 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide acquire affinity breadth through somatic mutations. Despite targeting conserved motif, only some show neutralizing activity in vitro against alpha- betacoronaviruses, including...
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...
Background & Aims: Immune targeting is likely required for functional cure of chronic hepatitis B (CHB). Tobevibart, a human monoclonal antibody against virus (HBV) surface antigen (HBsAg), neutralizes HBV and delta (HDV). This study aimed to characterize effects the engineered GAALIE Fc tobevibart on immune responses. Methods: We studied its equivalent HBC34*-GAALIE in vitro using electron microscopy, FcgR reporter cells, primary or mouse cells assess HBsAg binding, dendritic cell (DC)...
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...
The repeated spillovers of β-coronaviruses in humans along with the rapid emergence SARS-CoV-2 escape variants highlight need to develop broad coronavirus therapeutics and vaccines. Five monoclonal antibodies (mAbs) were isolated from COVID-19 convalescent individuals found cross-react multiple β-coronavirus spike (S) glycoproteins by targeting stem helix. One these mAbs, S2P6, cross-reacts more than twenty human animal S broadly neutralizes pseudotyped viruses sarbecovirus, merbecovirus...
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....
Abstract Coronaviruses use diverse Spike (S) glycoproteins to attach host receptors and fuse with target cells. Using a broad screening approach, we isolated from SARS-CoV-2 immune donors seven monoclonal antibodies (mAbs) that bind all human alpha beta coronavirus S proteins. These mAbs recognize the fusion peptide acquire high affinity breadth through somatic mutations. Despite targeting conserved motif, only some show neutralizing activity in vitro against coronaviruses, including Omicron...
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...