Dora Pinto
A5061263271- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
- Viral Infections and Immunology Research
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Viral Infections and Outbreaks Research
- Immunodeficiency and Autoimmune Disorders
- Bacillus and Francisella bacterial research
- HIV Research and Treatment
- Virus-based gene therapy research
- Chemokine receptors and signaling
- Escherichia coli research studies
- Single-cell and spatial transcriptomics
- Bacterial Infections and Vaccines
- Endoplasmic Reticulum Stress and Disease
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- Complement system in diseases
- Influenza Virus Research Studies
Vir Biotechnology (Switzerland)
2020-2024
VIR Biotechnology (United States)
2020-2022
Università della Svizzera italiana
2022
Scuola Cantonale di Commercio Bellinzona
2022
Instituto Gulbenkian de Ciência
2017
Istituto Superiore di Sanità
2010
Sapienza University of Rome
2007-2009
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera from recipients of BNT162b2 mRNA vaccine, we report impact on neutralization a panel authentic including B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes isogenic...
<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...
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....
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...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters elicit plasma-neutralizing against BA.1, BA.2, BA.2.12.1, and BA.4/5, breakthrough infections, but not vaccination alone, induce neutralizing the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells plasma of cases...
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded some areas by higher potential B1.1.7 variant now seen 50 countries. It unclear whether responses to SARS-CoV-2 vaccines based on prototypic strain will be impacted mutations found B.1.1.7. Here we assessed immune following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody a single immunization using pseudoviruses expressing wild-type...
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...
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...
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...
Abstract The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) B.1.1.7 (Alpha). In vitro , is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, 8-fold vaccine-elicited as compared wild type Wuhan-1 bearing D614G. Serum titres against were lower ChAdOx-1 versus BNT162b2 vaccinees. spike pseudotyped viruses exhibited...
SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths 1,2 . Vaccine therapeutic discovery efforts are paramount to curb spread of this zoonotic virus. The spike (S) glycoprotein promotes entry into host cells main target neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting S identified from memory B SARS survivor infected 2003. One antibody, named S309,...