Fabio Benigni
A5055585541- Urinary Bladder and Prostate Research
- SARS-CoV-2 and COVID-19 Research
- Cannabis and Cannabinoid Research
- Hormonal and reproductive studies
- Animal Virus Infections Studies
- Pelvic floor disorders treatments
- Bladder and Urothelial Cancer Treatments
- Urological Disorders and Treatments
- Viral gastroenteritis research and epidemiology
- Prostate Cancer Treatment and Research
- Sexual function and dysfunction studies
- Kidney Stones and Urolithiasis Treatments
- Immune Cell Function and Interaction
- Urinary and Genital Oncology Studies
- Adrenal Hormones and Disorders
- Stress Responses and Cortisol
- Immunotherapy and Immune Responses
- Hormonal Regulation and Hypertension
- COVID-19 Clinical Research Studies
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Neuroscience of respiration and sleep
- Immune Response and Inflammation
- Prostate Cancer Diagnosis and Treatment
- T-cell and B-cell Immunology
VIR Biotechnology (United States)
2022-2025
Vir Biotechnology (Switzerland)
2018-2024
Scuola Cantonale di Commercio Bellinzona
2022
Vita-Salute San Raffaele University
2012-2020
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2020
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2020
IRCCS Ospedale San Raffaele
2014-2018
Istituto Nazionale di Fisica Nucleare, Sezione di Milano
2012-2018
Montavid Thermodynamic Research Group
2018
University of Tsukuba
2018
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....
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...
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...
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...
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...
Cancer cells maintain a high glycolytic rate even in the presence of oxygen, phenomenon first described over 70 years ago and known historically as Warburg effect. Fructose 2,6-bisphosphate is powerful allosteric regulator glycolysis that acts to stimulate activity 6-phosphofructo-1-kinase (PFK-1), most important control point mammalian glycolysis. The steady state concentration fructose turn depends on enzyme 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase, which expressed...
IL-1 plays an important role in the pathophysiologic responses to infection and inflammation, part by mediating its own production that of other proinflammatory cytokines. However, relative contribution alpha beta inflammatory response has not been well clarified. Using beta-deficient (IL-1 -/-) mice, we investigated specific vivo vitro LPS. No differences between +/+ -/- mice were observed circulating levels for alpha, IL-6, or TNF-alpha after systemic administration either a low (5...
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...
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters result potent plasma neutralizing activity against BA.1 BA.2 breakthrough infections, but not vaccination-only, induce the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells of cases cross-react Wuhan-Hu-1, receptor-binding domains whereas...
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,...
The cytokine macrophage migration inhibitory factor (MIF) has emerged to be an important regulator of the inflammatory response and is critically involved in development septic shock, arthritis, glomerulonephritis. Although biological activities MIF are presumed require a receptor-based mechanism action, protein also tautomerase catalytically active N-terminal proline that invariant structurally homologous bacterial isomerases. This observation raises possibility may exert its action via...
Severe infection or tissue invasion can provoke a catabolic response, leading to severe metabolic derangement, cachexia, and even death. Macrophage migration inhibitory factor (MIF) is an important regulator of the host response infection. Released by various immune cells anterior pituitary gland, MIF plays critical role in systemic inflammatory counterregulating effect glucocorticoids on immune-cell activation proinflammatory cytokine production. We describe herein unexpected for regulation...
ABSTRACT The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a surface molecule that has been identified both human and murine polymorphonuclear neutrophils mature monocytes. activation of TREM-1 in the presence microbial components amplifies inflammatory response may be responsible for hyperresponsiveness observed during initial stage sepsis. To investigate effect modulation pathway experimental sepsis, we used analogue synthetic peptides derived from extracellular moiety...
Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells prostate (PCa) progression by sculpting TME. In a mouse PCa model, iNKT restrained pro-angiogenic immunosuppressive capabilities of tumor-infiltrating immune reducing TIE2+, M2-like macrophages (TEMs), sustaining pro-inflammatory M1-like macrophages. directly contacted stroma, cell transfer into tumor-bearing...
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...
Discovery of new actionable targets and functional networks in melanoma is an urgent need as only a fraction metastatic patients achieves durable clinical benefit by targeted therapy or immunotherapy approaches. Here we show that NFATc2 expression associated with EMT-like transcriptional program invasive phenotype, shown analysis cell lines at the mRNA protein levels, interrogation TCGA dataset characterization lesions immunohistochemistry. Gene silencing pharmacological inhibition...
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)...