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With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective antibody and T-cell responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with significantly higher purified yield than the Spike ectodomain. Squalene-in-water emulsion (SWE) formulated fusions were highly immunogenic. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant, while RBD-S2 fusions elicited broad neutralization including against the Clade 1a WIV-1 variant, and were highly efficacious. A lyophilized RBD-S2 fusion retained antigenicity and immunogenicity even after incubation at 37 °C for a month. In hamsters, SWE-formulated RBD-S2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations.

Organizations seeking to improve their performance, like Corporate Social Responsibility targets, face a key organisational design challenge. Designing the key components of the organization and their layout will have major impact on performances, and needs thus a robust design process. Organisation theory provides several models and methods to answer that need. Yet this design process has not been confronted to design methods literature, such as systematic design. The aim of this paper is to provide a synthesis of multiple theoretical elements coming from organization sciences, confronted with a classical engineering design model, to reveal similarities, differences and lacks of current literature on organization design. Our analysis of the available literature on organisation theory, organisation design and change management showed that this design process is close to systematic design, but we also highlighted several breaks in the design process, such as the lack of functional approach.

Product-service system (PSS) innovation is acknowledged as a promising way to achieve sustainability through better exploitation of given resources. Nevertheless, PSS implementation is also described as increasing failure risk for companies. Despite that authors have identified paradoxical situations as a source of failure while implementing PSS, few researches have focused on understanding the origin of these paradoxes. In this review, we aim at understanding how methodologies cope with the challenges of designing PSS throughout the complete company perimeter as well as how to manage interactions within this perimeter to avoid potential paradoxes and thus failure. To do so, we will rely on the business model innovation literature and, more specifically, the business model canvas to define and discretize the company perimeter. As for the interactions and their imbrication regarding paradoxes appearance, we will refer to Putnam et al. theory to gain deeper understanding of paradoxes-appearance mechanism. Our bibliometric strategy brought us to analyze 14 international articles via our graph, enabling us to highlight that some poles’ interactions during design are partly unaddressed, resulting potentially in the creation of tension sources and therefore potential paradoxes and ultimately implementation failure. Considering this, future research works could focus on defining all significant interactions to consider while designing a PSS as well as the typology of answers to engage while facing tensions. In that respect, these works could provide actionable solutions to lower PSS implementation-failure risk, thus benefiting those who wish to achieve better sustainability through PSS.

Through the decades, production planning activities have sought to balance market requirements and the optimal use of available resources in different industries. In the context of the Fourth Industrial Revolution, this study aims to disclose the purposes of production planning activities. To this end, this paper provides a literature review of the existing offer of production planning applications over the past 10 years. The authors propose a framework based on the objectives, scope and resources. The research conducted demonstrates that due to the uncertainty of the external environment, research propositions on production planning are focused on shorter planning horizons. The research also indicates that in order to face disruptions, production planning applications are mainly addressed to balance resource utilization. Ultimately, the study shows that a considerable part of innovative production planning applications have not yet been applied to real industrial cases, and moreover, they remain experimental propositions with no further use.

La Fabrication additive (FA) a pris une ampleur considerable depuis quelques annees. Le passage progressif des activites de prototypage vers celles de fabrication directe de pieces fonctionnelles remet en cause les methodes de conception et de fabrication traditionnelles, fondees sur les procedes conventionnels. Cet article fait le point sur les differentes technologies de FA et leurs champs d'utilisation tout au long du cycle de vie du produit. Les diverses applications industrielles sont decrites au travers d'exemples issus de secteurs technologiques de pointe.

Recent advances in human immunodeficiency virus (HIV) vaccine design have resulted in induction of strong CD4 T-cell proliferative and polyfunctional cytokine responses, which are also characteristic for long-term non-progressing (LTNP) HIV-infected individuals. However, limited information is available on the persistence of these responses after infection. Results from studies in non-human primates indicate that vaccine-induced immune responses are partially maintained upon viral infection and differ from the responses seen in non-vaccinated animals that typically progress to disease. However, it is unclear how these partially preserved responses compare to immune responses that are acquired naturally by LTNP animals. In this study, immune-response profiles were compared between vaccinated animals that, upon SHIV89.6p challenge, became infected but were able to control virus replication, and a group of animals having spontaneous control of this viral infection. Both groups were found to develop very similar immune responses with regard to induction of CD4 and CD8 T-cell polyfunctional cytokine responses, proliferative capacity and cytotoxic capacity, as measured by a standard 51Cr release assay and more direct ex vivo and in vivo CTL assays. Hence, vaccinated animals that become infected, but control infection, appear to establish immune responses that are similar to those elicited by long-term non-progressors.

The authors describe the production and characterization of a collection of Arabidopsis lines each carrying a transposed Ac (trAc) element. A total of 507 lines were obtained following germinal transpositions of a single Ac element located on the upper portion of chromosome III. Southern analysis revealed that up to 90% of the lines in this collection harbour distinct insertions of Ac in the Arabidopsis genome. As previous studies on the behaviour of Ac in Arabidopsis have indicated that approximately two out of three transposition events occur to linked loci, the authors hypothesized that this collection could be of great use in isolating insertional mutants for genes located in the vicinity of the donor locus. PCR and phenotypic screens were performed to identify mutations in five loci located within a 40 cm region of chromosome III centered on the donor locus. Molecular analyses confirmed the presence of germinal insertions of Ac in three of the loci (NPTII, ABI3 and EST #210A22). At a fourth locus (AtDMC1), despite the absence of a germinal insertion, one line in which somatic insertions occurred regularly was identified and may be of use in isolating a germinal insertion. This collection of trAc lines constitutes a useful complement to the existing collection of T-DNA insertion lines and will soon be made available through the Arabidopsis Biological Resource Center.

International audience; In order to remain competitive in an increasingly competitive international context, French companies are forced to follow one or more of various possible routes: relocating some of the activities, optimizing the design and / or production process, or innovate technologically. When they choose to develop new technologies, it is advisable to seek outside expertise in different areas. Thus they must exchange and create knowledge in partnership with other companies. But in order to control and integrate this future technology, we support that the acquisition and the capitalization of the technical training, during the process of innovation, are of primary importance. This article demonstrates that the construction of this knowledge base can be achieved only by formalizing close and rigorous collaboration. To do this, we propose a model of the collaborative process, meant for the leaders of innovative projects to support design.

International audience; Rapid prototyping machines are becoming faster at manufacturing machine tools. The processes of quality assurance impose the qualification of the production devices. A procedure and a test part are proposed for that purpose; intended for the family of processes of point-by-point layer manufacturing. Existing test parts only permit benchmarking and comparisons between machines: their capacity can be evaluated, but the test part analysis does not make it possible to establish the link between noted defects and their causes. The proposed process and test part permit the identification of the defects and whether their origins are machine or material linked. This paper describes the approach used to design the test part. Some preliminary measures were made on a test part, in order to discuss procedure and measurements.

International audience; Facing the increasing complexity of the product design area, (reduction of cycle times, introduction of simultaneous engineering, introduction of digital mock-up, ... ) a research department which wants to define a rapid prototyping process is confronted to the problem of the tools' choice. Therefore, we will propose in this article, a method allowing to conceive such a process. In a first chapter, we present the rapid prototyping area in the product design environment, in a second chapter we will propose our method illustrated by an industrial case.

For a majority of companies, innovation has become an essential element of corporate sustainability.However, during the product development phase the designer is forced to make decisions on design. These decisions subsequently have a strong impact on the acceptability of the products by the market. Orthopaedics implants design is no exception.The aim of this thesis is to show that it is possible to integrate, in the early phases of the orthopaedic implant development process, a tool for decision-making; in choosing concepts that incorporate technical, medical, surgical and economic criteria. The goal is to reduce the risk for the patient but also reduce the risk of commercial failure.The first part of this document focuses on analysing the context of this study, particularly for medical devices. Following this, the state of the art studies the various innovation processes and more specifically, the design process of medical orthopaedic implants. This work forced us to question and analyse evaluation methods for potential innovations available in the scientific literature, and integrate them into the implant sector.From this analysis, a question emerged lying at the heart of our research: how to design innovative implants with a low level of risk (clinical risk, default risk, risk of use)?The answer to this question has resulted in the proposal of a new tool for decision-making (Hypothesis 1) integrated within upstream phases of a suitable decision process (Hypothesis 2) for developing implants. These were then checked and validated in three experiments that resulted in the development of orthopaedic implants that were successfully inserted into patients.; Pour la plupart des entreprises, l’innovation est devenue un élément indispensable, garant de la pérennité de l’entreprise.Cependant, durant les phases de développement des produits, le concepteur est confronté lors des principaux jalons du processus à faire des choix de conception. Ces prises de décisions ont par la suite un fort impact sur l’acceptabilité ou non des produits par le marché. Le monde de la conception des implants orthopédiques n’y échappe pas.Le but de ce travail de thèse est de montrer qu’il est possible d’intégrer dans les phases amonts du processus de développement d’implants orthopédiques, un outil d’aide à la décision pour le choix de concepts intégrant des critères techniques, médicaux, chirurgicaux et économiques permettant de réduire les risques pour le patient mais aussi les risques d’un possible échec commercial.La première partie de ce document s’intéresse à l’analyse du contexte de cette étude et en particulier aux dispositifs médicaux. Ensuite, l’état de l’art étudie les différents processus d’innovation et plus spécifiquement les processus de conception dans le secteur médical des implants orthopédiques. Ces travaux nous ont amené à nous questionner et à analyser les méthodes d’évaluation du potentiel d’innovation disponibles au sein de la littérature scientifique, et de leur intégration au sein du secteur des implants.De cette analyse a émergé une question se situant au cœur de nos travaux de recherche : comment concevoir des implants innovants avec un niveau de risques faibles (risque clinique, risque de défaillance, risque d’utilisation) ?La réponse à cette question s’est traduite par la proposition d’un nouvel outil d’aide à la décision (hypothèse1) intégré aux phases amont d’un processus de conception adapté (hypothèse2) au développement d’implants. Celles-ci ont ensuite été vérifiées et validées lors de 3 expérimentations qui ont aboutis à la réalisation d’implants orthopédiques posés sur des patients.

For a majority of companies, innovation has become an essential element of corporate sustainability.However, during the product development phase the designer is forced to make decisions on design. These decisions subsequently have a strong impact on the acceptability of the products by the market. Orthopaedics implants design is no exception.The aim of this thesis is to show that it is possible to integrate, in the early phases of the orthopaedic implant development process, a tool for decision-making; in choosing concepts that incorporate technical, medical, surgical and economic criteria. The goal is to reduce the risk for the patient but also reduce the risk of commercial failure.The first part of this document focuses on analysing the context of this study, particularly for medical devices. Following this, the state of the art studies the various innovation processes and more specifically, the design process of medical orthopaedic implants. This work forced us to question and analyse evaluation methods for potential innovations available in the scientific literature, and integrate them into the implant sector.From this analysis, a question emerged lying at the heart of our research: how to design innovative implants with a low level of risk (clinical risk, default risk, risk of use)?The answer to this question has resulted in the proposal of a new tool for decision-making (Hypothesis 1) integrated within upstream phases of a suitable decision process (Hypothesis 2) for developing implants. These were then checked and validated in three experiments that resulted in the development of orthopaedic implants that were successfully inserted into patients.; Pour la plupart des entreprises, l’innovation est devenue un élément indispensable, garant de la pérennité de l’entreprise.Cependant, durant les phases de développement des produits, le concepteur est confronté lors des principaux jalons du processus à faire des choix de conception. Ces prises de décisions ont par la suite un fort impact sur l’acceptabilité ou non des produits par le marché. Le monde de la conception des implants orthopédiques n’y échappe pas.Le but de ce travail de thèse est de montrer qu’il est possible d’intégrer dans les phases amonts du processus de développement d’implants orthopédiques, un outil d’aide à la décision pour le choix de concepts intégrant des critères techniques, médicaux, chirurgicaux et économiques permettant de réduire les risques pour le patient mais aussi les risques d’un possible échec commercial.La première partie de ce document s’intéresse à l’analyse du contexte de cette étude et en particulier aux dispositifs médicaux. Ensuite, l’état de l’art étudie les différents processus d’innovation et plus spécifiquement les processus de conception dans le secteur médical des implants orthopédiques. Ces travaux nous ont amené à nous questionner et à analyser les méthodes d’évaluation du potentiel d’innovation disponibles au sein de la littérature scientifique, et de leur intégration au sein du secteur des implants.De cette analyse a émergé une question se situant au cœur de nos travaux de recherche : comment concevoir des implants innovants avec un niveau de risques faibles (risque clinique, risque de défaillance, risque d’utilisation) ?La réponse à cette question s’est traduite par la proposition d’un nouvel outil d’aide à la décision (hypothèse1) intégré aux phases amont d’un processus de conception adapté (hypothèse2) au développement d’implants. Celles-ci ont ensuite été vérifiées et validées lors de 3 expérimentations qui ont aboutis à la réalisation d’implants orthopédiques posés sur des patients.

L'expérimentation, outil de validation ou de confrontation de l'hypothèse à la réalité, nécessite des moyens spécifiques: les MOYENS D'EXPERIMENTATIONS (ME). Leur développement fait partie des programmes de recherche et d'innovation. Leur optimisation, en terme de coût, qualité et délai, est également un vecteur de compétitivité. Dans le cadre de cette thèse, notre étude se limite au développement des Moyens d'Expérimentations nouveaux et Spécifiques (MES) dans les domaines de recherche émergents et de l'innovation technologique. Après une enquête réalisée auprès de 21 laboratoires de recherche et de R&D en France plus une analyse d'environ trente projets de développement des MES réalisés de 1997 à 2002, nous constatons que: Le manque d'outils méthodologiques adaptés au contexte de développement et aux caractères spécifiques des MES ne permet pas d'affronter les difficultés de conception, source d'une qualité insuffisante. Les MES développés ne sont pas optimaux en terme de coût, de performance et de délai. Des recherches bibliographiques sur les méthodes et outils de conception de produits suivis d'une analyse de leur pertinence dans le contexte du développement des MES nous a permis de valider cette problématique. Notre ambition est d'optimiser le développement des Moyens d'Expérimentations avec l'objectif d'améliorer et de fiabiliser les MES et de rendre leur développement plus rationnel. Nous proposons une démarche de conception adaptée aux moyens d'expérimentations spécifiques. Cette démarche permet de mieux prendre en compte les particularités des MES et leur niveau de complexité, de faciliter les échanges entre le chercheur et le concepteur, et ainsi de concevoir un MES "bon du premier coup". La démarche est construite en intégrant deux nouveaux outils méthodologiques. Ils s'intitulent: "l'ANalyse de l'EXpérimentation Orientée Fonctionnelle" (ANEXOF) et "l'Analyse de la Cohérence en CoûtPerformance" (ACCP). L'ANEXOF exploite le besoin du chercheur et définit le cahier des charges fonctionnel. Elle est basée sur l'analyse fonctionnelle, associée à la démarche expérimentale, elle fait le lien entre les connaissances scientifiques du chercheur, les connaissances en conception et les savoir-faire technologiques du concepteur. L'ACCP intervient à partir de la phase de conception préliminaire dont le but est l'optimisation de la solution choisie. En réduisant au strict nécessaire les performances globales et en équilibrant leurs performances locales de façon cohérente avec leurs coûts, on obtiendra la répartition optimale de l'investissement dans sa structure, par conséquent, le coût global du produit est optimal.; pas de résumé.