A5067130944- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- DNA Repair Mechanisms
- HIV/AIDS drug development and treatment
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Carcinogens and Genotoxicity Assessment
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Viral Infections and Outbreaks Research
- Telomeres, Telomerase, and Senescence
- Hepatitis B Virus Studies
- Hepatitis Viruses Studies and Epidemiology
- vaccines and immunoinformatics approaches
- CRISPR and Genetic Engineering
- Hepatitis C virus research
- Inhalation and Respiratory Drug Delivery
- COVID-19 diagnosis using AI
- Poxvirus research and outbreaks
- Immune Cell Function and Interaction
- Virology and Viral Diseases
Inserm
2012-2025
Université Paris-Saclay
2019-2025
Infectious Disease Models and Innovative Therapies
2021-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2019-2024
CEA Paris-Saclay
2019-2024
Université Paris-Sud
2022-2023
CEA Paris-Saclay - Etablissement de Fontenay-aux-roses
2021-2023
Institut Cochin
2011-2018
Sorbonne Paris Cité
2016
Université Paris Cité
2011-2016
The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity mouse non-human primates following single injection confers complete from challenge macaques. Peak neutralizing antibody...
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...
Abstract The SARS-CoV-2 pandemic revealed the rapid evolution of circulating strains. This led to new variants carrying mostly mutations within receptor binding domain, which is immunodominant upon immunization and infection. In order steer immune response away from RBD epitopes more conserved domains, we generated S glycoprotein trimers without stabilized them by formaldehyde cross-linking. cryoEM structure demonstrated that SΔRBD folds into native prefusion conformation, one specific...
APOBEC3A (A3A), one of the seven-member APOBEC3 family cytidine deaminases, lacks strong antiviral activity against lentiviruses but is a potent inhibitor adeno-associated virus and endogenous retroelements. In this report, we characterize biochemical properties mammalian cell-produced catalytically active E. coli-produced A3A. The enzyme binds to single-stranded DNA with Kd 150 nM forms dimeric monomeric fractions. A3A, unlike APOBEC3G (A3G), deaminates substrates nonprocessively. Using...
The SARS-CoV2 Omicron variants have acquired new Spike mutations leading to escape from the most of currently available monoclonal antibody treatments reducing options for patients suffering severe Covid-19. Recently, both
ABSTRACT The HIV-1 Vpr protein participates in the early steps of virus life cycle by influencing accuracy reverse transcription. This role was related to recruitment nuclear form uracil DNA glycosylase (UNG2) enzyme into particles, but several conflicting findings have been reported regarding UNG2 encapsidation on viral infectivity. Here, we report that catalytic activity not required for mutation, and this function mapped within a 60-amino-acid domain located N-terminal region direct...
The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue impact the lives health of people across world for foreseeable future. rollout vaccines provided highly anticipated relief, but effective therapeutics are required further reduce risk severity infections. Monoclonal antibodies have been shown be as SARS-CoV-2, new variants concern (VoC) emerge, their utility use waned due limited or no efficacy against these variants. Furthermore, cumbersome...
The impact of variants concern (VoC) on SARS-CoV-2 viral dynamics remains poorly understood and essentially relies observational studies subject to various sorts biases. In contrast, experimental models infection constitute a powerful model perform controlled comparisons the observed with VoC better quantify how escape from immune response. Here we used molecular infectious load 78 cynomolgus macaques characterize in detail effects dynamics. We first developed mathematical that recapitulate...
Phospholipid Scramblase 1 (PLSCR1) was initially characterized as a type II transmembrane protein involved in bilayer movements of phospholipids across the plasma membrane leading to cell surface exposure phosphatidylserine, but other cellular functions have been ascribed this signaling processes and nucleus. In present study, expression PLSCR1 were explored specialized phagocytic cells monocyte/macrophage lineage. The found be markedly increased monocyte-derived macrophages compared...
Abstract The SARS-CoV2 Omicron variants have acquired new Spike mutations leading to escape from the most of currently available monoclonal antibody treatments reducing options for patients suffering severe Covid-19. Recently, both in vitro and vivo data suggested that Sotrovimab could retain partial activity against recent omicron sub-lineage such as BA.5 variants, including BQ.1.1. Here we report full efficacy BQ.1.1 viral replication measure by RT-qPCR a non-human primate challenge model.
HIV-1 Nef is essential for AIDS pathogenesis, but this viral protein not targeted by antiviral strategies. The functions of are largely related to perturbations intracellular trafficking and signaling pathways through leucine-based polyproline motifs that required interactions with clathrin-associated adaptor complexes SH3 domain-containing proteins, such as the phagocyte-specific kinase Hck. We previously described a single-domain antibody (sdAb) targeting inhibiting many, all, its...
Many toxic agents can cause DNA double strand breaks (DSBs), which are in most cases quickly repaired by the cellular machinery. Using ionising radiation, we explored kinetics of lesion signaling and structural chromosome aberration formation at intra- inter-chromosomal level. a novel approach, classic Premature Chromosome Condensation (PCC) was combined with γ-H2AX immunofluorescence staining order to unravel damage signalisation repair. We identified an early mechanism DSB joining that...
The targeting of HIV-1 using antibodies is high interest as molecular tools to better understand the biology virus or a first step toward design new inhibitors critical viral intracellular proteins. Small and highly stable llama-derived single-domain can often be functionally expressed in cytoplasm eukaryotic cells. Using selection method based on Sos Recruitment System, cytoplasmic yeast two-hybrid approach, we have isolated able bind Vpr Capside proteins cytoplasm. One anti-Vpr single...
The COVID-19 pandemic continues to have devastating consequences on health and economy, even after the approval of safe effective vaccines. Waning immunity, emergence variants concern, breakthrough infections, lack global vaccine access acceptance perpetuate epidemic. Here, we demonstrate that a single injection an adenoassociated virus (AAV)-based elicits at least 17-month-long neutralizing antibody responses in non-human primates levels were previously shown protect from viral challenge....
Due to the rapid evolution of SARS-CoV-2 variants with reduced sensitivity vaccine-induced humoral immunity and near complete loss protective efficacy licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection immunocompromised patient populations.
Through incorporation into virus particles, the HIV-1 Vpr protein participates in early steps of life cycle by influencing reverse transcription process. We previously showed that this positive impact on was related to binding uracil DNA glycosylase 2 enzyme (UNG2), leading enhancement infectivity established CD4-positive cell lines via a nonenzymatic mechanism.
Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool monitoring in this species. We investigated the benefit of computed X-ray tomography (CT) [18F]-FDG positron emission (PET) to monitor early phase disease large cohort (n = 76) infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at acute reflect heterogeneity burden following...
Abstract The SARS-CoV-2 Omicron variant exhibits very high levels of transmission, pronounced resistance to authorized therapeutic human monoclonal antibodies and reduced sensitivity vaccine-induced immunity. Here we describe P2G3, a antibody (mAb) isolated from previously infected vaccinated donor, which displays picomolar-range neutralizing activity against BA.1, BA.1.1, BA.2 all other current variants, is thus markedly more potent than or clinically advanced anti-SARS-CoV-2 mAbs....
Abstract Background Magnetic resonance imaging (MRI) is currently considered a safe technique because, unlike computed tomography, MRI does not expose patients to ionising radiation. However, conflicting literature reports possible genotoxic effects of MRI. We herein examine the chromosomal repeated scans by performing longitudinal follow-up integrity in volunteers. Methods This ethically approved study was performed on 13 healthy volunteers (mean age 33 years) exposed up 26 3-T sessions....
Abstract The rapid evolution of SARS-CoV-2 to variants with improved transmission efficiency and reduced sensitivity vaccine-induced humoral immunity has abolished the protective effect licensed therapeutic human monoclonal antibodies (mAbs). To fill this unmet medical need protect vulnerable patient populations, we isolated P4J15 mAb from a previously infected, vaccinated donor, <20 ng/ml neutralizing activity against all Omicron including latest XBB.2.3 EG.1 sub-lineages. Structural...
Abstract The impact of variants concern (VoC) on SARS-CoV-2 viral dynamics remains poorly understood and essentially relies observational studies subject to various sorts biases. In contrast, experimental models infection constitute a powerful model perform controlled comparisons the observed with VoC better quantify how escape from immune response. Here we used molecular infectious load 78 cynomolgus macaques characterize in detail effects dynamics. We first developed mathematical that...
PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after single dose. Here, we assessed immunogenicity following prime-boost regimen against SARS-CoV-2. In mice, low-dose prime followed by higher-dose boost elicited potent neutralizing antibody responses distinct cross-reactivity profiles, depending the antigen used booster vaccine. However, anti-vector developed mice...