Florian A. Lempp
A5018125417- Hepatitis B Virus Studies
- Hepatitis C virus research
- SARS-CoV-2 and COVID-19 Research
- Liver Disease Diagnosis and Treatment
- Animal Virus Infections Studies
- Hepatitis Viruses Studies and Epidemiology
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Viral Infections and Immunology Research
- Drug Transport and Resistance Mechanisms
- RNA Interference and Gene Delivery
- Viral Infections and Outbreaks Research
- Evolution and Genetic Dynamics
- Complement system in diseases
- CAR-T cell therapy research
- Liver physiology and pathology
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- Lung Cancer Research Studies
- Advanced Biosensing Techniques and Applications
- Eicosanoids and Hypertension Pharmacology
- Neutropenia and Cancer Infections
VIR Biotechnology (United States)
2020-2025
University Hospital Heidelberg
2014-2024
Heidelberg University
2014-2024
Vir Biotechnology (Switzerland)
2021-2024
University of San Francisco
2024
German Center for Infection Research
2016-2022
University of California, San Francisco
2022
European Foundation for the Study of Chronic Liver Failure
2016
Botkin Hospital
2015
Asser Institute
2015
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....
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...
SARS-CoV-2 evolution threatens vaccine- and natural infection-derived immunity as well the efficacy of therapeutic antibodies. To improve public health preparedness, we sought to predict which existing amino acid mutations in might contribute future variants concern. We tested predictive value features comprising epidemiology, evolution, immunology, neural network-based protein sequence modeling, identified primary biological drivers intra-pandemic evolution. found evidence that...
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...
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...
Background & Aims Current treatment for chronic hepatitis B virus (cHBV) infection requires lifelong treatment. New therapy aimed towards HBV functional cure would represent a clinically meaningful advancement. ALN-HBV and VIR-2218 (modified from by Enhanced Stabilization Chemistry Plus technology reducing off-target, seed-mediated binding while maintaining on-target antiviral activity) are investigational RNAi therapeutics that target all major transcripts. Methods We report the safety of...
Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B (HBV) not. It unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little known on how and HCV influence each other in coinfected cells. We investigated interactions between using HepaRG cells primary human hepatocytes (PHHs). analyzed effects of replication, vice versa, at single-cell level.PHHs were isolated from liver resection...
The Na + ‐taurocholate cotransporting polypeptide (NTCP) mediates uptake of conjugated bile acids (BAs) and is localized at the basolateral membrane hepatocytes. It has recently been recognized as receptor mediating hepatocyte‐specific entry hepatitis B virus delta virus. Myrcludex B, a peptide inhibitor entry, assumed to specifically target NTCP. Here, we investigated BA transport binding in first Slc10a1 ‐knockout mouse model ( encodes NTCP). Primary Slc10a1−/− hepatocytes showed absence...
Infections with the human hepatitis B virus (HBV) and D (HDV) depend on species‐specific host factors like receptor sodium taurocholate cotransporting polypeptide (hNTCP). Complementation of mouse hepatocytes hNTCP confers susceptibility to HDV but not HBV, indicating requirement additional HBV‐specific factors. As an essential premise toward establishment HBV‐susceptible animal model, we investigated role as a limiting factor in commonly used laboratory animals. Primary from mice, rats,...
Determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require the development well-standardized, reproducible antibody assays. This need has led to emergence a variety neutralization
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...
Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots 1 . Their impact on viral infection, transmission, and efficacy of vaccines therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. XBB.1 bind ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures the BQ.1.1 RBDs bound to human S309 Fab (sotrovimab parent) explain altered recognition...