The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies

The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs). The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans.Peer reviewe

Éditorial

À presque 40 ans, la revue Travail et Emploi était toujours parée des atours de ses 20 ans. Aussi avons-nous pensé qu’à l’âge de la plénitude, il était temps de lui insuffler une nouvelle énergie visuelle qui corresponde davantage à l’univers académique dans lequel elle s’inscrit. Fruit d’un travail collectif au sein du comité de rédaction, mais aussi avec la société qui l’a réalisée et a imaginé le graphisme de couverture, notre maquette modernisée marque une nouvelle étape dans la vie de la..

Development of Human-Like scFv-Fc Neutralizing Botulinum Neurotoxin E

Background Botulinum neurotoxins (BoNTs) are considered to be the most toxic substances known on earth and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food-poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNTs have been classified as category A agent by the Centers of Disease Control and Prevention (CDC) and are listed among the six agents with the highest risk to be used as bioweapons. Neutralizing antibodies are required for the development of effective anti-botulism therapies to deal with the potential risk of exposure. Results In this study, a macaque (Macaca fascicularis) was immunized with recombinant light chain of BoNT/E3 and an immune phage display library was constructed. After a multi-step panning, several antibody fragments (scFv, single chain fragment variable) with nanomolar affinities were isolated, that inhibited the endopeptidase activity of pure BoNT/E3 in vitro by targeting its light chain. Furthermore, three scFv were confirmed to neutralize BoNT/E3 induced paralysis in an ex vivo mouse phrenic nerve-hemidiaphragm assay. The most effective neutralization (20LD50/mL, BoNT/E3) was observed with scFv ELC18, with a minimum neutralizing concentration at 0.3 nM. Furthermore, ELC18 was highly effective in vivo when administered as an scFv-Fc construct. Complete protection of 1LD50 BoNT/E3 was observed with 1.6 ng/dose in the mouse flaccid paralysis assay. Conclusion These scFv-Fcs antibodies are the first recombinant antibodies neutralizing BoNT/E by targeting its light chain. The human-like nature of the isolated antibodies is predicting a good tolerance for further clinical development.Peer reviewe

The Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa

This paper reviews some research studies on tillage methods influencing soil and moisture conservation in the eastern African countries of Kenya, Tanzania, Malawi and Ethiopia during the past four decades. Most of these studies were conducted in marginal rainfall (semi arid ) areas and on shallow soils of various textures (sandy clay loam, sandy clay, clay and loam). The studies were meant to establish the effects of tillage and residue management practices on physico-chemical soil properties (i.e. structure, bulk density, soil moisture and organic matter contents), runoff and infiltration. This review emphasizes the importance of appropriate tillage and residue management methods (contour bunds and terraces, minimum tillage, tied ridging, mulching and conventional tillage) in providing soil conditions favourable for soil moisture conservation and subsequent crop performance and yield on smallholder farm

15 - Sous le care, le travail des femmes de milieux populaires. Pour une critique empirique d’une notion à succès

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Une mobilisation collective dans l'aide à domicile à la lumière des pratiques et des relations de travail

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Assistante maternelle, femme de ménage et aide à domicile : un retour au foyer ?

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Quel lien entre travail et classe sociale pour les travailleuses du bas de l’échelle ? L’exemple des aides à domicile auprès des personnes âgées dépendantes

La tertiarisation est souvent présentée comme l’une des sources de l’affaiblissement du lien entre travail et classe sociale, et donc de l’affaiblissement du caractère heuristique de cette dernière notion. Une étude ethnographique attentive à ce lien chez des aides à domicile permet de revenir sur ce constat. Dans cet emploi du bas de l’échelle, l’appartenance sociale est d’autant plus importante que ces femmes sont membres de strates différentes des classes populaires : les femmes issues des classes populaires stables font en sorte de se maintenir à distance des aspects les plus dévalorisants de leur métier; elles s’efforcent ainsi de dissocier leur statut social de leur métier. En revanche, les aides à domicile les plus précaires revendiquent leur investissement dans ce travail, en particulier la prise en charge de la dépendance, comme une forme de dignité personnelle.The development of the tertiary sector is often presented as one of the reasons for the weakening of a link between work and social class, and therefore the weakening of the heuristic use of this sociological concept. This proposition is examined via a detailed ethnographic study of home-care workers. The study finds that social standing is even more important in this lowly work. The women are from different social strata of the popular classes. Those who enjoy a stable position within this group manage to distance themselves from the most degrading aspects of the work, thereby separating social status and work. In contrast, home-care workers who have a more precarious social standing find a form of personal dignity in their investments in this work and in particular their care for dependent persons

: Spécifier une position sociale : quelles opérations de recherche ?

International audienc

Recursos y divisiones sociales en el trabajo de cuidado. ¿Qué operaciones son necesarias para la investigación de una posición social?

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