The mechanistic target of rapamycin (mTOR) positively regulates multiple steps of the HIV-1 replication cycle. We previously reported that a 12-week supplementation of antiretroviral therapy (ART) with metformin, an indirect mTOR inhibitor used in type-2 diabetes treatment, reduced mTOR activation and HIV transcription in colon-infiltrating CD4 T cells, together with systemic inflammation in nondiabetic people with HIV-1 (PWH). Herein, we investigated the antiviral mechanisms of metformin.
View Article and Find Full Text PDFPredicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 spike protein mimicked a vaccine boost by inducing a massive amplification of spike-specific memory B cells, plasmablast differentiation, and spike-specific antibody secretion.
View Article and Find Full Text PDFAntibodies play a pivotal role in protecting from SARS-CoV-2 infection, but their efficacy is challenged by the continuous emergence of viral variants. In this study, we describe two broadly neutralizing antibodies cloned from the memory B cells of a single convalescent individual after infection with ancestral SARS-CoV-2. Cv2.
View Article and Find Full Text PDFBackground: SARS-CoV-2 Omicron lineage contains variants with multiple sequence mutations relative to the ancestral strain particularly in the viral spike gene. These mutations are associated inter alia with loss of neutralization sensitivity to sera generated by immunization with vaccines targeting ancestral strains or prior infection with circulating (non-Omicron) variants. Here we present a comparison of vaccine formulation elicited cross neutralization responses using two different assay readouts from a subpopulation of a Phase II/III clinical trial.
View Article and Find Full Text PDFThe unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.
View Article and Find Full Text PDFThe mechanistic target of rapamycin (mTOR) positively regulates multiple steps of the HIV-1 replication cycle. We previously reported that a 12-weeks supplementation of antiretroviral therapy (ART) with metformin, an indirect mTOR inhibitor used in type-2 diabetes treatment, reduced mTOR activation and HIV transcription in colon-infiltrating CD4 T-cells, together with systemic inflammation in nondiabetic people with HIV-1 (PWH). Herein, we investigated the antiviral mechanisms of metformin.
View Article and Find Full Text PDFSARS-CoV-2 variants with undetermined properties have emerged intermittently throughout the COVID-19 pandemic. Some variants possess unique phenotypes and mutations which allow further characterization of viral evolution and Spike functions. Around 1,100 cases of the B.
View Article and Find Full Text PDFThe unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.
View Article and Find Full Text PDFAntibodies effective against the recent Omicron sublineages are missing. By taking advantage of a multi-centric prospective cohort of immunocompromised individuals treated for mild-to-moderate COVID-19, Bruel et al. show that administration of 500 mg of sotrovimab induces serum neutralization and antibody-dependent cellular cytotoxicity of BQ.
View Article and Find Full Text PDFBecause SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concern (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralization capacity was measured longitudinally against all main VoCs.
View Article and Find Full Text PDFBackground: Monoclonal antibodies (mAbs) targeting the spike of SARS-CoV-2 prevent severe COVID-19. Omicron subvariants BQ.1.
View Article and Find Full Text PDFBackgroundThe risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.MethodsTo correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity.
View Article and Find Full Text PDFMpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals.
View Article and Find Full Text PDFThe emergence of Omicron sublineages impacts the therapeutic efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs). Here, we evaluate neutralization and antibody-dependent cellular cytotoxicity (ADCC) activities of 6 therapeutic mAbs against Delta, BA.2, BA.
View Article and Find Full Text PDFBackground: Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.
View Article and Find Full Text PDFBackground: The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised.
Methods: In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples.
Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination.
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