A5009031768- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Toxoplasma gondii Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Parasitic Infections and Diagnostics
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- HIV-related health complications and treatments
- Calpain Protease Function and Regulation
- Advanced Biosensing Techniques and Applications
- interferon and immune responses
- Antibiotic Resistance in Bacteria
- Blood groups and transfusion
- Synthesis and Characterization of Heterocyclic Compounds
- Trypanosoma species research and implications
- Venomous Animal Envenomation and Studies
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Genetics and Neurodevelopmental Disorders
University of Zurich
2012-2025
Institute of Virology of the Slovak Academy of Sciences
2021
University of Geneva
2007-2012
Institut Jacques Monod
2008
Sorbonne Université
2008
Université Paris Cité
2008
Centre National de la Recherche Scientifique
2008
CEA Paris-Saclay
2008
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2008
Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that enriched individuals elite breadth. Analyzing over 65,000 sequences from CATNAP database, AMP trials, longitudinal cohorts (SHCS, ZPHI, CAPRISA), we found variants extra Cys present low levels fluctuate time....
Numerous intracellular pathogens exploit cell surface glycoconjugates for host recognition and entry. Unlike bacteria viruses, Toxoplasma gondii other parasites of the phylum Apicomplexa actively invade cells, this process critically depends on adhesins (microneme proteins) released onto parasite from organelles called micronemes (MIC). The microneme adhesive repeat (MAR) domain T. MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant invasion by pathogen. By complementation assays,...
Host cell invasion by the Apicomplexa critically relies on regulated secretion of transmembrane micronemal proteins (TM-MICs). Toxoplasma gondii possesses functionally non-redundant MIC complexes that participate in gliding motility, host attachment, moving junction formation, rhoptry and invasion. The TM-MICs are released onto parasite's surface as capable interacting with receptors. Additionally, TgMIC2 simultaneously connects to actomyosin system via binding aldolase. During these...
For use in prevention and treatment, HIV-1 broadly neutralizing antibodies (bnAbs) have to overcome Env conformational heterogeneity of viral quasispecies neutralize with constant high potency. Comparative analysis neutralization data from the CATNAP database revealed a nuanced relationship between bnAb activity flexibility, substantial epitope-specific variation potency ranging increased decreased against open, neutralization-sensitive Env. To systematically investigate impact variability...
The eukaryotic mismatch repair (MMR) protein MSH6 exhibits a core region structurally and functionally similar to bacterial MutS. However, it possesses an additional N-terminal (NTR), comprising PCNA binding motif, large of unknown function nonspecific DNA fragment. Yeast NTR was recently described as extended tether between the . In contrast, we show that human presents globular PWWP domain in function. We demonstrate this binds double-stranded DNA, without any preference for mismatches or...
Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large cohort screen. By establishing comprehensive signatures based on IgG1, IgG2, IgG3 activity 13 antigens 4,281 individuals the same cohort, we now show four are significantly linked neutralization breadth, namely viral load, infection length, diversity,...
The HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion viral and cellular membranes. Here, we present the crystal structure gp41 locked intermediate state by an MPER-specific neutralizing antibody. illustrates plasticity six membrane anchors arranged asymmetrically with peptides transmembrane regions pointing into different directions. Hinge located adjacent peptide region facilitate flexibility that allows high-affinity binding...
Abstract The intracellular protozoan Toxoplasma gondii is among the most widespread parasites. broad host cell range of parasite can be explained by carbohydrate microarray screening analyses that have demonstrated ability T. adhesive protein, TgMIC1, to bind a wide spectrum sialyl oligosaccharide ligands. Here, we investigate further in dose‐response format differential binding TgMIC1 2‐3‐ and 2‐6‐linked carbohydrates. Interestingly, two novel synthetic fluorinated analogs 3′SiaLacNAc 1–4...
ABSTRACT Here, we applied the designed ankyrin repeat protein (DARPin) technology to develop novel gp120-directed binding molecules with HIV entry-inhibiting capacity. DARPins are interesting for envelope inhibitor design, as their high-affinity differs from that of antibodies. in general prefer epitopes a defined folded structure. We probed whether this capacity favors selection gp120-reactive specificities epitope recognition and inhibitory activity differ those found among neutralizing...
During the entry process, human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer undergoes a sequence of conformational changes triggered by both CD4 and coreceptor engagement. Resolving conformation these transient intermediates has proven challenging. Here, we fine-mapped antigenicity induced increasing engagement cell surface–expressed Env. Escalating triggering led to sequential adoption different pre-fusion states Env trimer, up pre-hairpin conformation, that...
Abstract The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target V3-base. Challenging this view, we present V3-crown Designed Ankyrin Repeat Proteins (bnDs) matching breadth V3-base bnAbs. While most bnAbs prefusion Env, bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve focusing on highly conserved residues that are accessible...
The monitoring and assessment of a broadly neutralizing antibody (bnAb) based HIV-1 vaccine require detailed measurements binding responses to support the detection correlates protection. Here we describe development flexible, high-throughput microsphere multiplex assay system that allows complex signatures. Studying panel 13 antigens in parallel different IgG subclasses (IgG1, IgG2 IgG3) demonstrate potential our strategy. technical advances include means improve antigen reactivity using...
Abstract The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for cell entry. Conformational masking of V3 within allows efficient neutralization via only by rare, broadly neutralizing glycan-dependent antibodies targeting closed prefusion but not abundant that access crown open trimers after CD4 attachment. Here, we report a distinct category V3-specific inhibitors based designed ankyrin repeat protein (DARPin) technology...
Summary The identification of HIV-1 Envelope glycoprotein (Env) traits associated with development neutralization cross-reactivity in natural infection is critical for vaccine design. Here we describe the presence additional Cysteine (Cys) residues V1 that are enriched among people elite breadth. Using >65,000 sequences from CATNAP database, AMP trials and three large longitudinal HIV cohorts, SHCS, ZPHI CAPRISA studies, show Env variants extra Cys present at low levels throughout...
The ability of broadly neutralizing antibodies (bnAbs) to interact with the closed, pre-fusion HIV-1 envelope (Env) trimer distinguishes them from weakly (weak-nAbs) that depend on opening bind. Comparative analysis neutralization data CATNAP database revealed a nuanced relationship between bnAb activity and Env conformational plasticity, substantial epitope-specific variation potency ranging increased decreased against open, neutralization-sensitive Env. To systematically investigate impact...
Abstract Broadly neutralizing antibodies (bnAbs) recognizing a diversity of HIV-1 strains are widely thought to be essential for an vaccine. Extensive knowledge on bnAbs has been gained from studying natural HIV infection by following bnAb evolution in individual people with (PWH). However, it remains increase responses large PWH cohorts assess the feasibility inducing activity vaccination. To allow systematic analysis, we created XbnAb cohort, bnAb-inducer cohort selected screening plasma...
Abstract The HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion viral and cellular membranes. Here, we present the crystal structure gp41 locked intermediate state by an MPER-specific neutralizing antibody. illustrates plasticity six membrane anchors arranged asymmetrically with peptides transmembrane regions pointing into different directions. Hinge located adjacent peptide region facilitate flexibility that allows high affinity...
Abstract Understanding the balance between epitope shielding and accessibility on HIV-1 envelope (Env) trimers is essential to guide immunogen selection for broadly neutralizing antibody (bnAb) based vaccines. To investigate antigenic space of Env immunogens, we created a strategy synthetic, high diversity, Designed Ankyrin Repeat Protein (DARPin) libraries. We show that DARPin Antigenicity Analysis (DANA), purely in vitro screening tool, has capability extrapolate relevant information...