Laura E. Rosen
A5011844851- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- Protein Structure and Dynamics
- Viral gastroenteritis research and epidemiology
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- vaccines and immunoinformatics approaches
- Viral Infections and Immunology Research
- Bacterial Genetics and Biotechnology
- Hepatitis B Virus Studies
- Bacillus and Francisella bacterial research
- Influenza Virus Research Studies
- Respiratory viral infections research
- Virus-based gene therapy research
- Hepatitis C virus research
- Mass Spectrometry Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 detection and testing
- Viral Infections and Outbreaks Research
- CRISPR and Genetic Engineering
- Complement system in diseases
- Hepatitis Viruses Studies and Epidemiology
- Protein purification and stability
VIR Biotechnology (United States)
2020-2025
Vir Biotechnology (Switzerland)
2025
University of California, San Francisco
2019
University of California, Berkeley
2014-2015
QB3
2013-2015
Berkeley College
2014
Pomona College
2006
Fred Hutch Cancer Center
2006
<h2>Summary</h2> SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines antibody therapeutics. Here, we demonstrate that the immunodominant spike (S) receptor binding motif (RBM) is a highly variable region S provide epidemiological, clinical, molecular characterization prevalent, sentinel RBM mutation, N439K. We N439K protein has enhanced affinity to hACE2 receptor, viruses have similar <i>in vitro</i> replication fitness cause infections clinical...
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...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation numerous spike mutations. To understand the antigenic shift, we determined cryo–electron microscopy and x-ray crystal structures protein receptor-binding domain bound broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb sotrovimab) human ACE2 receptor. We...
An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape
A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I the signal peptide, W152C N-terminal domain (NTD), and L452R receptor-binding (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or convalescent exhibited neutralizing titers that were reduced 2- to 3.5-fold against B.1.427/B.1.429 relative wild-type pseudoviruses. The mutation activity 14 34...
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....
How the Delta variant evades defenses In course of COVID-19 epidemic, variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, some which evade immunity or increase transmission. late 2020, and Kappa were detected, became globally dominant by June 2021. McCallum et al . show that vaccine-elicited serum-neutralizing activity is reduced against these variants. Based on biochemistry structural studies, authors mutations in domain binds ACE2 receptor abrogate...
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...
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation characterization of a human monoclonal antibody, designated S2K146, that neutralizes viruses belonging SARS-CoV- SARS-CoV-2-related clades which use ACE2 as an entry receptor. Structural functional studies show most virus residues directly bind S2K146 are also involved in binding ACE2. This allows...
SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains receptor-binding domain (RBD) and N-terminal (NTD) as two main targets of neutralizing antibodies (Abs). A novel variant concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California currently spreading throughout US 29 additional countries. It unclear whether antibody responses to infection or prototypic Wuhan-1 isolate-based vaccines will be impacted three B.1.427/B.1.429 S mutations: S13I,...
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...
Rapidly evolving influenza A viruses (IAVs) and B (IBVs) are major causes of recurrent lower respiratory tract infections. Current vaccines elicit antibodies predominantly to the highly variable head region haemagglutinin their effectiveness is limited by viral drift1 suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits enzymatic activity all group 1 2 IAVs, as well Victoria/2/87-like, Yamagata/16/88-like ancestral IBVs....
The kinetic folding of ribonuclease H was studied by hydrogen exchange (HX) pulse labeling with analysis an advanced fragment separation mass spectrometry technology. results show that proceeds through distinct intermediates in a stepwise pathway sequentially incorporates cooperative native-like structural elements to build the native protein. Each step is seen as concerted transition one or more segments from HX-unprotected HX-protected state. Deconvolution data near amino acid resolution...
SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that immunodominant spike (S) receptor binding motif (RBM) is most divergent region S, provide epidemiological, clinical, molecular characterization a prevalent RBM variant, N439K. We N439K S protein has enhanced affinity hACE2 receptor, virus similar clinical outcomes in vitro replication fitness as compared wild- type. observed mutation resulted...
SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted largest fraction of neutralizing antibodies (Abs) in COVID-19 patient plasma. Little known about Abs binding to epitopes outside RBD and their contribution protection. Here, we describe 41 human monoclonal (mAbs) derived from memory B cells, which recognize S N-terminal (NTD) show a subset them neutralize ultrapotently. We define antigenic map...
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,...
Worldwide SARS-CoV-2 transmission leads to the recurrent emergence of variants, such as recently described B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.2+ (delta+). The variant concern is causing a new wave infections in many countries, mostly affecting unvaccinated individuals, has become globally dominant. We show that these variants dampen vitro potency vaccine-elicited serum neutralizing antibodies provide structural framework for describing impact individual mutations on immune...
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are receptor-binding domain (RBD), thereby raising concerns about effectiveness available vaccines and antibody therapeutics. Here, we show that RBD binds to human ACE2 with enhanced affinity relative Wuhan-Hu-1 acquires binding mouse ACE2. Severe reductions plasma neutralizing activity were observed against compared ancestral pseudovirus for vaccinated convalescent...
Chronic hepatitis B is a global public health problem, and coinfection with delta virus (HDV) worsens disease outcome. Here, we describe (HBV) surface antigen (HBsAg)-targeting monoclonal antibody (mAb) the potential to treat chronic D.HBsAg-specific mAbs were isolated from memory cells of HBV vaccinated individuals. In vitro neutralization was determined against HDV enveloped HBsAg representing eight genotypes. Human liver-chimeric mice treated twice weekly candidate mAb starting 3 weeks...
Homing endonucleases are highly specific enzymes, capable of recognizing and cleaving unique DNA sequences in complex genomes. Since such cleavage events can result targeted allele-inactivation and/or allele-replacement vivo, the ability to engineer homing matched interest would enable powerful precise genome manipulations. We have taken a step-wise genetic approach analyzing individual endonuclease I-CreI protein/DNA contacts, describe here novel interactions at four distinct target site...