A5037631225- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Reproductive System and Pregnancy
- SARS-CoV-2 detection and testing
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Immune Cell Function and Interaction
- COVID-19 Impact on Reproduction
- COVID-19 epidemiological studies
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Reproductive tract infections research
- Preterm Birth and Chorioamnionitis
- Pregnancy and Medication Impact
- Immune Response and Inflammation
- Infectious Encephalopathies and Encephalitis
- Virus-based gene therapy research
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- S100 Proteins and Annexins
- Herpesvirus Infections and Treatments
- Pelvic floor disorders treatments
- HIV/AIDS Research and Interventions
- Animal Virus Infections Studies
Université Paris-Saclay
2020-2024
CEA Paris-Saclay
2020-2024
Inserm
2006-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014-2024
Infectious Disease Models and Innovative Therapies
2014-2024
CEA Paris-Saclay - Etablissement de Fontenay-aux-roses
2014-2024
Université Paris-Sud
2015-2023
Centre International de Recherche en Infectiologie
2020
Virologie et Pathologies Humaines
2020
Université Claude Bernard Lyon 1
2020
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there an urgent need for a vaccine that prevents viral infection, transmission, disease. Here, we present two-component protein-based nanoparticle displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show this induces potent neutralizing antibody responses in mice, rabbits, cynomolgus macaques....
Significance Human γδ T lymphocytes have innate-like and adaptive-like functions can circulate in blood or reside tissues. They are activated by specific antigens recognized their T-cell receptor recognize infected transformed cells, suggesting that cellular stress is involved antigen expression. However, molecular characterization of stress-induced remains elusive, hampering our understanding the role cells cancer infections. In present study we identify annexin A2 as such known a...
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...
Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics 31 cynomolgus macaques for which nasopharyngeal and tracheal load were frequently assessed. We identified that cells had large burst size (>10 4 virus) within-host reproductive basic number of approximately 6 compartment, respectively. After peak load, rapidly lost half-life 9 hours, no significant association between cytokine elevation...
Abstract Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent B.1.1.7 isolate. In both settings, SARS-CoV-2 remains undetectable lungs treated hACE2 mice. Therapeutic treatment also causes reduction viral loads Syrian hamsters. When administered at 10 mg kg-1...
Abstract The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising vitro results to successful clinical implementation. Among the drugs have been largely tested trials but failed so far bring clear evidence of efficacy favipiravir, a nucleoside analogue with spectrum activity against several RNA viruses and small models. Here, we evaluate antiviral favipiravir Zika or SARS-CoV-2 virus cynomolgus macaques. In both models, high...
Nipah virus (NiV) has been recently ranked by the World Health Organization as being among top eight emerging pathogens likely to cause major epidemics, whereas no therapeutics or vaccines have yet approved. We report a method deliver immunogenic epitopes from NiV through targeting of CD40 receptor antigen-presenting cells fusing selected humanized anti-CD40 monoclonal antibody glycoprotein with conserved fusion and nucleocapsid peptides. In African green monkey model, CD40.NiV induces...
During the first trimester of human pregnancy, Natural Killer (NK) cells maternal uterine mucosa (e.g. decidua) have a unique phenotype and are involved in crucial physiological processes during pregnancy. We investigated whether modifications NK receptor repertoire occur found significantly decreased expression KIR2DL1/S1 KIR2DL2/L3/S2 receptors, NKp30 NKp44 activatory CD85j (ILT-2) inhibitory receptor. also observed increased NKG2D at decidual cell surface. By flow cytometry, we further...
During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite permissivity placenta and decidua (the uterine mucosa during pregnancy) to infection. In from macrophages (dMs) are main target cells. Decidual natural killer (dNK) cells account for 70 % decidual leukocytes. They display distinct phenotype functions compared peripheral NK At periphery, involved control this study, we investigate whether human dM infection.Autologous cocultures infected dMs with dNK reveal...
Maternofetal pathogen transmission is partially controlled at the level of maternal uterine mucosa fetal implantation site (the decidua basalis), where and cells are in close contact. Toll-like receptors (TLRs) may play an important role initiating rapid immune responses against pathogens basalis, however tolerant microenvironment should be preserved order to allow development. Here we investigated expression functionality TLRs expressed by decidual macrophages (dMs) NK (dNKs), major cell...
Abstract COVID-19 has become a pandemic that caused over 200,000 deaths worldwide, with no antiviral drug or vaccine yet available. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs have demonstrated in vitro . Among these candidates, hydroxychloroquine (HCQ) been given thousands individuals worldwide but definitive evidence for HCQ treatment is still missing.We evaluated activity both and SARS-CoV-2-infected macaques. showed monkey African green kidney...
Abstract Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children pregnant women. Here, we present a new generation of subunit targeting antigens CD40-expressing antigen-presenting cells. We demonstrate that the receptor-binding domain (RBD) spike protein CD40 (αCD40.RBD) induces significant...
Abstract The characterization of vaccine distribution to relevant tissues after in vivo administration is critical understanding their mechanisms action. Vaccines based on mRNA lipid nanoparticles (LNPs) are now being widely considered against infectious diseases and cancer. Here, we used imaging approaches compare the trafficking two LNP formulations encapsulating following intramuscular administration: DLin-MC3-DMA (MC3) recently developed DOG-IM4. formulated DOG-IM4 LNPs persisted at...
In order to develop strategies prevent HIV-1 (human immunodeficiency virus type 1) transmission, it is crucial better characterize target cells in the female reproductive tract (FRT) mucosae and identify effective innate responses. Control of infection decidua (the uterine mucosa during pregnancy) can serve as a model study natural mucosal protection. Macrophages are main decidua. Here we report that vitro, macrophages T targets endometrium nonpregnant women. As reported for decidual (dM),...
Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic P2X7 NLRP3 are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with disease 2019 (COVID-19) reveal expression is increased in targets of including alveolar macrophages, type II pneumocytes...
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
Background Chlamydiosis, a sexually transmitted infection (STI) induced by Chlamydia trachomatis (CT), increases local inflammation (cytokine production, recruitment of immune cells such as neutrophils). Few is known on the impact CT phenotype cervicovaginal neutrophils. Vaginal microbiota (VM) key factor in regulation responses and STI acquisition where Lactobacillus spp are associated with protection. In this study, VM cynomolgus macaques was enriched crispatus after metronidazole...
The female reproductive tract (FRT) is the main site of entry sexually transmitted infections (STIs). Toll-Like receptors (TLRs) that recognize pathogenic motifs are widely expressed in FRT. TLR stimulation induces immune activation and local production inflammatory mediators. In FRT, this response should also be compatible with functions symbiosis host microbiota . With a view to develop efficient mucosal vaccines prevent STI acquisition, role ligands FRT needs explored. We have therefore...
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...
Abstract Background Maternofetal transmission (MFT) of HIV-1 is relatively rare during the first trimester pregnancy despite permissivity placental cells for cell-to-cell infection. Invasive interact directly with decidual uterine mucosa months pregnancy, but role decidua in control unknown. Results We found that mononuclear naturally produce low levels IL-10, IL-12, IL-15, TNF-α, IFN-α, IFN-γ and CXCL-12 (SDF-1), large amounts CCL-2 (MCP1), CCL-3 (MIP-1α), CCL-4 (MIP-1β), CCL-5 (Rantes),...
The composition of the microbiota in cynomolgus macaques is only partially characterized, although this animal model often used to study pathogenesis and preventive strategies against infections. We thus performed, for first time, a longitudinal characterization vaginal rectal five cycling female macaques. Samples were collected weekly 15 weeks V3/V4 regions the16S rRNA gene sequenced. Sequences analyzed with QIIME OTU detection taxonomic assignment. Progesterone levels also determined...
The definition of correlates protection is critical for the development next-generation SARS-CoV-2 vaccine platforms. Here, we propose a model-based approach identifying mechanistic based on mathematical modelling viral dynamics and data mining immunological markers. application to three different studies in non-human primates evaluating vaccines CD40-targeting, two-component spike nanoparticle mRNA 1273 identifies quantifies two main mechanisms that are decrease rate cell infection an...