A5041949062- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- COVID-19 Clinical Research Studies
- Virology and Viral Diseases
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Bacteriophages and microbial interactions
- Vaccine Coverage and Hesitancy
- Autophagy in Disease and Therapy
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- COVID-19 epidemiological studies
- Respiratory viral infections research
- Cancer Immunotherapy and Biomarkers
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Animal Virus Infections Studies
- Dermatology and Skin Diseases
- Immune Response and Inflammation
- Viral Infections and Outbreaks Research
Sorbonne Université
2010-2025
Inserm
2014-2025
Centre National de la Recherche Scientifique
2014-2025
Institut Mondor de Recherche Biomédicale
2017-2025
Institut de Recherche Vaccinale
2015-2025
Université Paris-Est Créteil
2019-2025
Centre d'Immunologie et des Maladies Infectieuses
2014-2025
Université Paris Cité
2017
University of California, Berkeley
2005-2010
Institut Pasteur
2003-2009
Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing ability activate immune responses. How DC function is maintained light this paradox not understood. By analyzing susceptibility primary human subsets infections, we report that CD141+ DCs have an innate resistance infection by a broad range enveloped viruses, including HIV influenza virus. In...
The development of ribosomal profiling (Riboseq) revealed the immense coding capacity human and viral genomes. Here, we used Riboseq to delineate translatome HIV-1 in infected CD4+ T cells. In addition canonical protein sequences (CDSs), identify 98 alternative open reading frames (ARFs), corresponding small Open Reading Frames (sORFs) that are distributed across HIV genome including UTR regions. Using a database genomes, observe most ARF amino-acid likely conserved among clade B C HIV-1,...
Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered differentiation Tfh isolated from lymph nodes HIV-infected (HIV+) individuals provide inadequate help in vitro. However, the mechanisms underlying this impairment function are not fully defined. Using a unique collection splenocytes, we compared frequency, phenotype transcriptome subsets spleens HIV negative...
Abstract It is widely assumed that CD4+ T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)–restricted Ags have been described, in particular epitopes newly synthesized proteins (so-called endogenous). In this study, we show HIV-infected dendritic (DC) present MHC-II–restricted endogenous to HIV-specific (HS) cells. This pathway functions independently the exogenous route...
To determine the contribution of skin DC subsets in regulation humoral immunity, we used a well-characterized antigen targeting system to limit availability and presentation certain skin-derived subsets. Here show that delivery foreign steady state Langerhans cells (LCs) cDC1s through same receptor (Langerin) led to, respectively, robust versus minimal-to-null immune response. LCs, unlike cDC1s, supported formation germinal center T follicular helper (GC-Tfh) dose-dependently then, likely...
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...
Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative frames (ARFs) potentially encoding small polypeptides. We have identified a panel of ARFs within gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes...
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...
CD8+ T cells recognize HIV-1 epitopes translated from a gene's primary reading frame (F1) and any one of its five alternative frames (ARFs) in the forward (F2, F3) or reverse (R1-3) directions. The 3' end HIV-1's proviral coding strand contains conserved sequence that is directly overlapping but antiparallel to env gene (ARF R2) encodes for putative antisense protein called ASP. ASP expression has been demonstrated vitro using HIV-transfected cell lines infected cells. Although antibodies...
Human epidermal and mucosal Langerhans cells (LCs) express the C-type lectin receptor langerin that functions as a pattern recognition receptor. LCs are among first immune to interact with HIV-1 during sexual transmission. In this study, we demonstrate not only but also an adhesion mediating clustering between dendritic (DCs). Langerin recognized hyaluronic acid on DCs removal of these carbohydrate structures partially abrogated LC-DC clustering. Because did cross-present HIV-1-derived Ags...
There is an urgent need of a new generation vaccine that are able to enhance protection against SARS-CoV-2 and related variants concern (VOC) emerging coronaviruses.We identified conserved T- B-cell epitopes from Spike (S) Nucleocapsid (N) highly homologous 38 sarbecoviruses, including VOCs, design protein subunit targeting antigens Dendritic Cells (DC) via CD40 surface receptor (CD40.CoV2).CD40.CoV2 immunization elicited high levels cross-neutralizing antibodies SARS-CoV-2, SARS-CoV-1 in...
Cytotoxic T cells detect intracellular pathogens by surveying peptide loaded MHC class I molecules (pMHC I) on the cell surface. Effective immune surveillance also requires infected to present pMHC promptly before viral progeny can escape. Rapid presentation apparently occurs because synthesize and peptides from antigenic precursors called defective ribosomal products (DRiPs). The molecular characteristics of DRiPs are not known.Here, using a novel method for detecting proteolytic...
Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from proteins, but also cryptic encoded by alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape CTLs targeting one such epitope, Q9VF, an HIVgag ARF and presented HLA-B*07. Using PBMCs patients, we first cloned sequenced proviral DNA encoding for Q9VF. identified several polymorphisms with minority proviruses...
The development of HIV-1 vaccines is challenged by the lack relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with hematopoietic stem cells (hu-mice), B cell-development function are impaired fail efficiently transition from IgM IgG cells. Here, we found that CD40-targeted vaccination combined CpG-B adjuvant overcomes usual defect B-cell switch maturation hu-mice. We further dissected hu-B cell directed against Env protein...
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...
Objective: To investigate the ability of granulocyte-macrophage colony-stimulating factor (GM–CSF) and IFN-α to induce differentiation peripheral monocytes into dendritic cells (DC) their trigger an HIV-specific CD8 T-cell response. Methods: Monocytes isolated from both seronegative controls HIV-infected individuals were differentiated DC using GM–CSF with either IL-4 or for 7 days. We assessed phenotypic characteristics IL-12 production by flow cytometry. The responses was means ELISpot...
Abstract Purpose: The human telomerase reverse transcriptase (hTERT) is considered as a potential target for cancer immunotherapy because it preferentially expressed in tumor cells. To increase the applicability of hTERT-based immunotherapy, we set out to identify CTL epitopes hTERT restricted by HLA-B*0702 molecule, common MHC class I allele. Experimental Design: HLA-B*0702-restricted peptides from were selected using method epitope prediction and tested their immunogenicity (in vitro)...
A variety of signals influence the capacity dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C-type lectines, influences DC biology affects their susceptibility HIV infection. Yet, whether combined effects PPRs triggering infection HIV-specific (HS) CTL responses remain enigmatic. Here, we dissect impact receptors on maturation, infection, quality HS activation....