A5079307726- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- interferon and immune responses
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Inflammasome and immune disorders
- RNA modifications and cancer
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- Autoimmune and Inflammatory Disorders Research
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Animal Virus Infections Studies
- RNA Research and Splicing
- Lymphoma Diagnosis and Treatment
- IL-33, ST2, and ILC Pathways
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Head and Neck Cancer Studies
- Renal Transplantation Outcomes and Treatments
QB3
2015-2024
University of California, Los Angeles
2015-2024
VIR Biotechnology (United States)
2020-2024
Genmab (Netherlands)
2024
University of San Francisco
2024
Vir Biotechnology (Switzerland)
2020-2022
University of California, San Francisco
2022
Synthetic Genomics (United States)
2019-2022
University of California System
2018
Singapore Immunology Network
2011-2016
<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...
Antibody-dependent enhancement (ADE) of disease is a general concern for the development vaccines and antibody therapies because mechanisms that underlie protection against any virus have theoretical potential to amplify infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in pandemic coronavirus 2019 (COVID-19), which caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Here we review observations relevant risks ADE...
Interferons interfere with lung repair (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), engage various functions. Type I IFNs (IFN-α and IFN-β) widely expressed can result immunopathology during viral infections. By contrast, type III (IFN-λ) responses primarily restricted mucosal surfaces thought confer protection without driving damaging proinflammatory responses. Accordingly, IFN-λ...
Abstract Monocytes promote the early host response to infection releasing key pro-inflammatory cytokines, such as IL-1β. The biologically inactive IL-1β precursor is processed active form by inflammasomes, multi-protein complexes activating caspase-1. Human monocytes exhibit an unconventional one-step pathway of inflammasome activation in lipopolysaccharide (LPS) alone. Although this lineage-restricted mechanism likely contribute pathology endotoxin shock, signalling pathways regulating are...
Significance Cancer cells can be recognized and attacked by CD8 + cytolytic T cells, but tumor-infiltrating often become functionally incompetent (“exhausted”) fail to destroy tumor cells. We show that T-cell exhaustion requires antigen recognition By examining the transcriptional chromatin accessibility profiles of antigen-reactive -unreactive we confirm our previous conclusion transcription factor NFAT promotes identify Nr4a factors as new targets for future investigation. anti–PD-L1...
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 coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role interferons (IFNs) type I (IFN-I) or III (IFN-III) families remains debated. We scrutinized production IFNs along respiratory tract COVID-19 patients and found that high levels IFN-III, to a lesser extent IFN-I, characterize upper airways with viral burden reduced risk severity. Production specific not members denotes mild pathology efficiently drives transcription genes protect...
Timing cues epigenomic reprogramming Different temporal dynamics of activation the transcription factor nuclear κB (NF-κB) can influence inflammatory response activated macrophages. Cheng et al. report a mechanism by which oscillatory and sustained NF-κB signaling may produce distinct transcriptional responses (see Perspective Nandagopal ). Oscillatory poised enhancers to transcribe genes in mouse However, produced cells other stimuli acted on epigenome. These relieved chromatin silencing at...
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....
To evaluate the frequency of distant metastases (DM) and to determine ability certain clinical pathologic factors predict development metastases.Retrospective analysis.University hospital.A total 1972 patients with oral, oropharyngeal, hypopharyngeal, laryngeal squamous cell carcinomas who were treated from 1981 1998 not diagnosed as having DM at time initial treatment.We evaluated influence different variables in their appearance.A 181 (9.2%) (95% confidence interval, 7.9%-10.5%) developed...
The complement system is a potent component of the innate immune response, promoting inflammation and orchestrating defense against pathogens. However, dysregulation critical to several autoimmune inflammatory syndromes. Elevated expression proinflammatory cytokine IL-1β often linked such diseases. In this study, we reveal mechanistic link between secretion using murine dendritic cells. occurs following intracellular caspase-1 activation by inflammasomes. We show that elicits both IL-18 in...
In the context of lung transplant (LT), because diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate impact AMR on prognosis. diagnosis requires association clinical symptoms, donor-specific antibodies (DSAs), and C4d+ staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, positive (DSAposAMRpos); (ii)...
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 Regulatory T cell (Treg) therapy is a promising approach for transplant rejection and severe autoimmunity. Unfortunately, clinically meaningful Treg numbers can be obtained only upon in vitro culture. Functional stability of human expanded (e)Tregs induced (i)Tregs has not been thoroughly addressed all proposed protocols, hindering clinical translation. We undertook systematic comparison eTregs iTregs to recommend the most suitable implementation, then tested their effectiveness...
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,...
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,...
Abstract Profiling immunoglobulin (Ig) receptor repertoires with specialized assays can be cost-ineffective and time-consuming. Here we report ImReP, a computational method for rapid accurate profiling of the Ig repertoire, including complementary-determining region 3 (CDR3), using regular RNA sequencing data such as those from 8,555 samples across 53 tissues types 544 individuals in Genotype-Tissue Expression (GTEx v6) project. Using ImReP GTEx v6 data, generate collection 3.6 million...
Abstract Traditional antibody optimization approaches involve screening a small subset of the available sequence space, often resulting in drug candidates with suboptimal binding affinity, developability or immunogenicity. Based on two distinct antibodies, we demonstrate that deep contextual language models trained high-throughput affinity data can quantitatively predict unseen variants. These variants span K D range three orders magnitude over large mutational space. Our reveal strong...