Recent advances in developing specific therapies for haemophilia

Haemophilia therapy has undergone very rapid evolution in the last 10 years. The major limitation of current replacement therapy is the short half-life of factors VIII and IX. These half-lives have been extended by the addition of various moieties, allowing less frequent infusion regimens. Entirely novel approaches have also entered the clinic, including a bispecific antibody that mimics factor VIII and strategies that rebalance the haemostatic mechanism by reducing antithrombin through inhibition of synthesis. These two treatments are available by subcutaneous injection at infrequent intervals and both can be used in patients with neutralising antibodies (inhibitors). Finally, a cure may be on the horizon with preliminary evidence of success for gene therapy in haemophilia B and A

Influence de couvertures de kikuyu (Pennisetum clandestinum) et lotier (Lotus uliginosus) sur les propriétés physiques, chimiques et biologiques des andosols

L'auteur présente un dispositif expérimental localisé dans les Hauts de l'ouest de la Réunion, à plus de 600 m d'altitude, dans une zone essentiellement volcanique (20 000 ha dont 9 000 à vocation agricole). Les cultures étudiées sont le géranium rosat, le maïs, la tomate, mais surtout le haricot. Les observations et analyses ont porté sur les profils, la macrofaune du sol, la relance de l'activité biologique, la conductivité hydraulique, la fertilité chimique. La lutte contre l'érosion et la restructuration des terres dégradées par insuffisance ou absence de couverture végétale constitue la toile de fond de cette étude expérimental

Utilisation du modèle STREAM pour raisonner les aménagements fonciers

In the Pays de Caux, runoff on crop fields is at the origin of important disturbances in frequency and costs, such as ephemeral gully erosion, muddy flows and turbidity of drinking water. As most of the slopes are gentle (< 3%), water circulation thus strongly depends on the shape, limits and tillage direction of fields. Since 1997, in the operations of land development, techniques are proposed and realized to limit erosive runoff. Within the framework of such an operation in progress in a catchment area of 501 ha, STREAM was used to locate areas where the runoff is likely to concentrate and thus to determine suitable sites for control measures. After obtaining input data, STREAM made it possible to compare the runoff patterns and volumes before and after land consolidation and that for several spring and winter rainfall events with return periods of from 2 to 20 years. Graphic results highlight modifications of the runoff network on the plateau, due to the changes of fields’ limits and size. Since land use remained unchanged, there is no significant difference in runoff volumes at the outlet of the catchment area. On the other hand, on the plateau, STREAM highlights important local modifications related for example to the removal of a meadow (50% more runoff). STREAM also made it possible to test the impact of the installation of two new ponds on runoff. Results show that the use of STREAM during an operation of land development can be useful, and they also make it possible to determine under which conditions it is a tool to aid engineering and design department decision making. It makes it possible to identify the assets of existing field pattern in order to preserve them in the project and test the new field pattern at the stage of the preliminary draft in order to estimate its impact on the runoff. The engineering and design department can then propose soil protection measures or modify the initial project

Design and testing of a global positioning system-based radiometer for precision mapping of pearl millet total dry matter in the Sahel

The nondestructive determination of plant total dry matter (TDM) in the field is greatly preferable to the harvest of entire plots in areas such as the Sahel where small differences in soil properties may cause large differences in crop growth within short distances. Existing equipment to nondestructively determine TDM is either expensive or unreliable, Therefore, two radiometers for measuring reflected red and near-infrared light were designed, mounted on a single wheeled hand cart and attached to a differential Global Positioning System (GPS) to measure georeferenced variations in normalized difference vegetation index (NDVI) in pearl millet fields [Pennisetum glaucam (L.) R. Br.]. The NDVI measurements were then used to determine the distribution of crop TDM. The two versions of the radiometer could (i) send single NDVI measurements to the GPS data logger at distance intervals of 0.03 to 8.53 m set by the user, and (ii) collect NDVI values averaged across 0.5, I, or 2 m. The average correlation between TDM of pearl millet plants in planting hills and their NDVI values was high (r(2) = 0.850) but varied slightly depending on solar irradiance when the instrument was calibrated. There also mas a good correlation between NDVI, fractional vegetation cover derived from aerial photographs and millet TDM at harvest Both versions of the rugged instrument appear to pro tide a rapid and reliable way of mapping plant growth at the field scale with a high spatial resolution and should therefore be widely tested with different crops and soil types

XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants

International audienceAmino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBMs), in direct contact sites with the angiotensin converting enzyme-2 (ACE-2). Therefore, in Spike/ACE-2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study on Vero E6 cells conducted over 1 month, no mutation was associated with the addition of increasing doses of XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE-2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19) including the different variants of concern identified so far

LIS1, a glyco-humanized swine polyclonal anti-lymphocyte globulin, as a novel induction treatment in solid organ transplantation

International audienceAnti-thymocyte or anti-lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because animal-derived, ATGs/ALGs contain highly immunogenic carbohydrate xenoantigens eliciting antibodies that are associated with subclinical inflammatory events, possibly impacting long-term graft survival. Their strong and long-lasting lymphodepleting activity also increases the risk for infections. We investigated here the in vitro and in vivo activity of LIS1, a glyco-humanized ALG (GH-ALG) produced in pigs knocked out for the two major xeno-antigens αGal and Neu5Gc. It differs from other ATGs/ALGs by its mechanism of action excluding antibody-dependent cell-mediated cytotoxicity and being restricted to complement-mediated cytotoxicity, phagocyte-mediated cytotoxicity, apoptosis and antigen masking, resulting in profound inhibition of T-cell alloreactivity in mixed leucocyte reactions. Preclinical evaluation in non-human primates showed that GH-ALG dramatically reduced CD4 + (p=0.0005,***), CD8 + effector T cells (p=0.0002,***) or myeloid cells (p=0.0007,***) but not T-reg (p=0.65, ns) or B cells (p=0.65, ns). Compared with rabbit ATG, GH-ALG induced transient depletion (less than one week) of target T cells in the peripheral blood (&lt;100 lymphocytes/L) but was equivalent in preventing allograft rejection in a skin allograft model. The novel therapeutic modality of GH-ALG might present advantages in induction treatment during organ transplantation by shortening the T-cell depletion period while maintaining adequate immunosuppression and reducing immunogenicity