A5026870722- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Hemoglobin structure and function
- Viral Infections and Immunology Research
- Systemic Lupus Erythematosus Research
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Single-cell and spatial transcriptomics
- Drug-Induced Adverse Reactions
- Urticaria and Related Conditions
- Electron Spin Resonance Studies
- Protein Interaction Studies and Fluorescence Analysis
- COVID-19 epidemiological studies
- Cell Image Analysis Techniques
University Hospital of Lausanne
2015-2025
University of Lausanne
2015-2025
SIB Swiss Institute of Bioinformatics
2024
Weatherford College
2024
Swiss Vaccine Research Institute
2019-2022
Institut de Recherche Vaccinale
2020-2021
ENT and Allergy
2021
Boehringer Ingelheim (Canada)
2012-2016
Howard Hughes Medical Institute
2000
Yale University
2000
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the immunity is associated with bias toward granulopoiesis bone marrow hematopoietic progenitor but it unknown whether BCG vaccination also leads to functional reprogramming mature neutrophils. Here, we show healthy...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses to the spike (S) protein monomer, S native trimeric form, or nucleocapsid (N) proteins were evaluated in cohorts of individuals with infection (n = 93) and enrolled a postinfection seroprevalence population study 578) Switzerland. Commercial assays specific for S1 N protein, within newly developed Luminex assay using trimer found be equally sensitive detection acute-infection-phase samples....
Abstract The objective of the present study was to identify biological signatures severe coronavirus disease 2019 (COVID-19) predictive admission in intensive care unit (ICU). Over 170 immunological markers were investigated a ‘discovery’ cohort (n = 98 patients) Lausanne University Hospital (LUH-1). Here we report that 13 out 49 cytokines significantly associated with ICU three cohorts ( P < 0.05 0.001), while cellular lacked power discriminating between and non-ICU patients. cytokine...
An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with 1 established importance C3 C4 substituent antiviral potency against viruses different aa124/aa125 variants IN. The C7 position on serum shifted established. Introduction a quinoline at provided balance metabolic stability. Combination these findings ultimately led discovery 26 (BI 224436), first NCINI advance...
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load types remains unknown. Comprehensive and deep analysis circulating tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8
ABSTRACT BI 224436 is an HIV-1 integrase inhibitor with effective antiviral activity that acts through a mechanism distinct from of strand transfer inhibitors (INSTIs). This 3-quinolineacetic acid derivative series was identified using enzymatic long terminal repeat (LTR) DNA 3′-processing assay. A combination medicinal chemistry, parallel synthesis, and structure-guided drug design led to the identification as candidate for preclinical profiling. It has 50% concentrations (EC 50 s) <15...
Abstract Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light the attractiveness developing SCFA-mediated therapies and considering that SCFAs work as inhibitors histone deacetylases which are known to interfere with defenses. Here we show propionate, one main SCFAs, dampens response innate immune cells microbial stimulation,...
The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum an individual indicates previous infection or vaccination. However, it provides limited insight into protective nature this immune response. Neutralizing recognizing viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that costly, time-consuming, inflexible, potentially biohazardous. Here, we present a cell-free...
There are limited comparative data on the durability of neutralizing antibody (nAb) responses elicited by messenger RNA (mRNA) vaccines against SARS-CoV-2 variants concern (VOCs) in immunocompromised patients and healthy controls.
Background Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography–CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value ICI-related myocarditis, especially at early stage, limited. Thus, we investigated 68...
Although gut and lymph node (LN) memory CD4 T cells represent major HIV simian immunodeficiency virus (SIV) tissue reservoirs, the study of role dendritic (DCs) in persistence has long been limited to blood due difficulties access lymphoid samples. In this study, we show that LN migratory resident DC subpopulations harbor distinct phenotypic transcriptomic profiles. Interestingly, both contain intact provirus inducible replication-competent despite expression antiviral restriction factor...
Chimeric antigen receptor (CAR) T-cell therapy is the standard of care for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, more than half patients fail to achieve durable remission. Identifying predictive biomarkers within CAR infusion product (IP) may guide strategies improve clinical outcomes. This single-center observational study conducted at Lausanne University Hospital (CHUV), Switzerland, analyzed IPs from 13 with R/R DLBCL who underwent standard-of-care...
Highlights•bNAb LN01 neutralizes 92% of a 118-strain virus panel•LN01 targets the HIV-1 gp41 MPER, TM region, and lipids•LN01-complexed MPER forms continuous helix with TM•Most paratope residues interacting MPER-TM lipids are germline encodedSummaryPotent broadly neutralizing antibodies (bnAbs) hallmark protection by vaccination. The membrane-proximal external region (MPER) fusion protein is targeted most reactive antibodies. Here, we examine structural molecular mechansims neutralization...
Control of the ongoing SARS-CoV-2 pandemic is endangered by emergence viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity vaccine-induced immunity. Here, we screen B cells from COVID-19 donors identify P5C3, a highly potent broadly neutralizing monoclonal antibody picomolar activity against all concern (VOCs) identified date. Structural characterization P5C3 Fab in complex spike demonstrates defined large buried...
Abstract The SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and less sensitive vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from previously infected vaccinated donor showed that it picomolar-range neutralizing activity BA.1, BA.1.1, BA.2 all other variants tested. We solved the structure Fab in complex with spike using...
<h3>Background and Objective</h3> Depleting CD20<sup>+</sup> B cells is the primary mechanism by which ocrelizumab (OCRE) efficient in persons with multiple sclerosis (pwMS). However, exact role of OCRE on other immune cell subsets directly or indirectly remains elusive. The purpose this study to characterize dynamics peripheral pwMS OCRE. <h3>Methods</h3> We collected blood samples from 38 before onset (T0) at 6 12 months (T6, T12) after initiation. To cover diversity, using mass cytometry...
Abstract Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of immunological factors that promote durable protection. Here we apply systems vaccinology investigate antibody responses in adolescents Netherlands (N = 14; NL) and United Kingdom 12; UK) receiving tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report early...
For more than five years, high-dimensional mass cytometry has been employed to study immunology. However, these studies have typically performed in one laboratory on or few instruments. We present the results of a six-center using healthy control human peripheral blood mononuclear cells (PBMCs) and commercially available reagents test intra-site inter-site variation cytometers operators. used prestained controls generated by primary center as reference compare against samples stained at each...
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by multiple cellular and molecular dysfunctions of the innate adaptive immunity. Cytotoxic function NK cells compromised in patients with SLE. Herein, we phenotypic alterations SLE comprehensive manner to further delineate mechanisms underlying cytotoxic dysfunction identify novel potential therapeutic targets. Therefore, examined PBMC from matched healthy controls single-cell mass cytometry assess phenotype...
Abstract To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA IgG in representative population-based cohort 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop maintain anti-S responses. In subsample 64 participants, further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, T cell Membrane (M), N,...
Small guanosine triphosphatases, typified by the mammalian Ras proteins, play major roles in regulation of numerous cellular pathways. A subclass evolutionarily conserved Ras-like proteins was identified, members which differ from other containing amino acids at positions 12 and 61 that are similar to those present oncogenic forms Ras. These κB-Ras1 κB-Ras2, interact with PEST domains IκBα IκBβ [inhibitors transcription factor nuclear kappa B (NF-κB)] decrease their rate degradation. In...