Biology subjects

Delbue, S.

Publications and source records attributed to Delbue, S..

4 recordsLinked to original sources

bioRxiv2025

A Highly Potent Human Antibody Neutralizing All Serotypes of BK Polyomavirus

BK polyomavirus infection poses a significant risk to kidney transplant recipients. Reactivation of dormant virus in the transplanted kidney, triggered by immunosuppression, can lead to BK polyomavirus-associated nephropathy in up to 10% of transplants, often resulting in loss of graft function or even graft loss. Currently, there is no specific treatment that reliably prevents BK polyomavirus-associated nephropathy or halts its progression. Standard of care relies on reducing immunosuppression, allowing the immune system to gradually control the infection but at the risk of provoking rejection episodes and compromising kidney function. This study describes the discovery and characterization of an ultra-potent BK polyomavirus-neutralizing antibody, identified from a kidney transplant recipient who displayed rapid clearance of high-level BK viremia. Antibody mAb 319C07 (USAN potravitug) neutralizes all four BK polyomavirus serotypes and recognizes an epitope critical for viral cell attachment. mAb 319C07 is in clinical development for the treatment of BKPyV infection in renal transplant patients (NCT05769582).

immunology↗

bioRxiv2022

Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir - an orally available inhibitor of the 3-chymotrypsin-like cysteine protease - has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

immunology↗

bioRxiv2021

Broad antiviral effects of Echinacea purpurea against SARS-CoV-2 variants of concern and potential mechanism of action

BackgroundSARS-CoV-2 variants of concern (VOC) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Some exhibit increased pathogenicity and transmissibility compared to the original wild type WUHAN (Hu-1). Broad-spectrum antivirals could complement and further enhance preventive benefits achieved through SARS-CoV-2 vaccination campaigns MethodsThe anti-coronavirus activity of Echinacea purpurea (Echinaforce(R) extract, EF) against (i) VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish) and B1.525 (eta), (ii) SARS-CoV-2 spike (S) protein-pseudotyped viral particles and reference strain OC43 as well as (iii) wild-type SARS-CoV-2 (Hu-1) were analyzed. Molecular dynamics (MD) were applied to study interaction of Echinaceas phytochemical markers with known pharmacological viral and host cell targets. ResultsEF extract broadly inhibited propagation of all investigated SARS-CoV-2 VOCs as well as entry of SARS-CoV-2 pseudoparticles at EC50s ranging from 3.62 to 12.03 {micro}g/ml. Preventive addition of 20 {micro}g/ml EF to epithelial cells significantly reduced sequential infection with SARS-CoV-2 (Hu-1) as well as with the common human strain OC43. MD analyses showed constant binding affinities to Hu-1, B1.1.7, B.1.351, P.1 and B1.617.2-typic S protein variants for alkylamides, caftaric acidand feruoyl-tartaric acid in EF extract. They further indicated that the EF extract could possibly interact with TMPRSS-2, a serine protease required for virus endocytosis. ConclusionsEF extract demonstrated stable antiviral activity across 6 tested VOCs, which is likely due to the constant affinity of the contained phytochemical marker substances to all spike variants. A possible interaction of EF with TMPRSS-2 partially would explain cell protective benefits of the extract by inhibition of endocytosis. EF may therefore offer a supportive addition to vaccination endeavors in the control of existing and future SARS-CoV-2 virus mutations.

microbiology↗

bioRxiv2021

Controlled administration of aerosolized SARS-CoV-2 to K18-hACE2 transgenic mice uncouples respiratory infection and anosmia from fatal neuroinvasion

The development of a tractable small animal model faithfully reproducing human COVID-19 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ACE2 in epithelial cells (K18-hACE2 transgenic mice) that are intranasally instilled with a liquid SARS-CoV-2 suspension under deep anesthesia. Unfortunately, this experimental approach results in disproportionate high CNS infection leading to fatal encephalitis, which is rarely observed in humans and severely limits this models usefulness. Here, we describe the use of an inhalation tower system that allows exposure of unanesthetized mice to aerosolized virus under controlled conditions. Aerosol exposure of K18-hACE2 transgenic mice to SARS-CoV-2 resulted in robust viral replication in the respiratory tract, anosmia, and airway obstruction, but did not lead to fatal viral neuroinvasion. When compared to intranasal inoculation, aerosol infection resulted in a more pronounced lung pathology including increased immune infiltration, fibrin deposition and a transcriptional signature comparable to that observed in SARS-CoV-2- infected patients. This model may prove useful for studies of viral transmission, disease pathogenesis (including long-term consequences of SARS-CoV-2 infection) and therapeutic interventions.

immunology↗