This thesis’s main purpose is to understand the recent debate in Sweden concerning the vaccine passport that was caused due to the recent spread of the corona virus. The focus is on what a variety of arguments and positions from different public political debaters have taken in a number of issues regarding vaccine passports. If they have been ideologically consistent regarding their previous ideologic positions in other debates in Sweden. First the thesis describes the three main ideologies used (liberalism, socialism and conservatism) and outlines their main positions. By doing so, the thesis can later compare what Swedish opinion leaders have argued in regards to the vaccine passport and therefore find out if they are relatable to their main ideology.  This has been made possible by the implementation of the design of an Ide whose purpose is to investigate and try to understand why different sides of this debate think about how they think about vaccine passports along with if it seems consistent.. The result points to that it can indeed be found ideological inconsistencies in some varieties. For example, if opinion leaders affiliated with the liberal ideology finding the vaccine passports useful might seem to clash with the main positions of the liberal ideology.

Bakgrund: Desinformation kring vaccination kan leda till ökad misstro mot hälsomyndigheter och undergräva folkhälsoresponsen. Vaccintveksamhet bland medicinsk personal är särskilt problematiskt då de ofta ses av allmänheten som medicinskt sakkunniga, och deras inställning till vaccinet kan avsevärt bidra till allmänhetens vaccinationsvilja. Att undersöka vaccinationsviljan och dess faktorer är relevant för att kunna hitta strategier för att främja vaccinationstäckningen. Syfte: Att beskriva vaccinationsvilja hos olika professioner inom vården samt vilka faktorer som påverkat den individuella vaccinationsviljan. Metod: Semistrukturerade intervjuer gjordes utifrån ett snöbollsurval. Sammanfattningsvis deltog totalt 5 sjuksköterskor, 2 undersköterskor och 2 medicinska sekreterare i studien, samtliga verksamma på sjukhus. Som metod för analys av det insamlade materialet valdes kvalitativ innehållsanalys. Resultat: Vaccinationsvilja är beroende av faktorer som etnicitet, yrkesroll, politisk tillhörighet, kunskapsnivå om svårighetsgraden av Covid-19 och vaccinets effektivitet. Vaccinationsbeslut förknippas med etisk stress och en känsla av tvång och otrygghet. Myndigheterna anses inte vara transparanta i sin kommunikation och det finns en stor oro i att delar av viktig information utelämnas. De som vaccinerat sig gjorde det av solidaritet, för att bidra till pandemins slut och för att de ville skydda sina patienter, sin familj och sina vänner. Bruket av sociala medier har ökat under pandemin, för att hålla kontakt med vänner och familj, men även för att hitta hälsoinformation. Slutsats: Kunskap kring vaccin och hur de fungerar är inte en självklar del av utbildningen bland de professioner som deltog i studien. Vårdpersonal måste ges kunskaper för att tryggt och faktabaserat kunna diskutera denna viktiga fråga med patienter då rekommendationer kring vaccin måste tydliggöras. Eftersom informationen ska tas emot av människor med stora variationer i ålder, utbildning och förkunskaper kan det vara lämpligt att skala ner den biomedicinska utbildningsstrategin och istället rikta in hälsokommunikationen på en kulturell och politisk bakgrund för att diskutera hälsofrämjande åtgärder som vaccination. / Background: Misinformation about vaccination can lead to increased mistrust of health authorities and undermine the public health response. Vaccinehesitancy among medical staff is particularly problematic as they are often seen by the public as medical experts, and their attitude to the vaccine can significantly contribute to the public's willingness to get vaccinated. Examining the willingness to get vaccinated and its factors is relevant in order to be able to find strategies to promote vaccination coverage. Aim: To describe the willingness to get vaccinated against Covid-19 among different professions in healthcare and what factors have influenced their determination to get vaccinated. Method: Semi-structured interviews were conducted based on a snowball selection. In summary, a total of 5 nurses, 2 assistant nurses and 2 medical secretaries participated in the study, all active in hospitals. Qualitative content analysis was chosen as the method for analysis of the collected material. Results: Acceptance of vaccines depends on factors such as ethnicity, professional role, political affiliation, level of knowledge about the severity of Covid-19 and the vaccine's effectiveness. Vaccination decisions are associated with ethical stress, coercion and insecurity. The authorities are not considered to be transparent in their communication and there is great concern that parts of important information are omitted. Those who accepted the vaccine did so out of solidarity, to help end the pandemic and to protect their patients, family and friends. The use of social media has increased during the pandemic, to keep in touch with friends and family, but also to find health information. Conclusion: Knowledge about vaccines and how they work is not an obvious part of the education among the professions that participated in the study. Nursing staff must be given knowledge to be able to safely and fact-based discuss this important issue with patients as recommendations regarding vaccines must be clarified. As the information is to be received by people with large variations in age, education and prior knowledge, it may be appropriate to scale down the biomedical education strategy and instead focus health communication on a cultural and political background to discuss health promotion measures such as vaccination.

La tuberculose (TB), maladie pulmonaire causée par le Mycobacterium tuberculosis (Mtb), reste la première cause de mortalité par un agent infectieux. La TB est responsable de près de 1,7 million de morts et de 10,4 millions de nouveaux cas par an dans le monde. L’émergence et la propagation de souches bactériennes multi-résistantes aux antibiotiques (MDR) représentent une menace majeure grandissante et reflètent l’efficacité partielle des thérapies actuelles. Le traitement des patients atteints de TB-MDR est constitué actuellement de combinaisons d’antibiotiques, souvent toxiques, administrés pendant une longue durée, avec une efficacité limitée. Il existe donc un besoin urgent de développer de nouveaux traitements antituberculeux. L’immunothérapie, dont l’objectif est d’améliorer la réponse immunitaire de l’hôte contre le Mtb, représente une approche complémentaire intéressante dans le but de diminuer la durée et d’augmenter l’efficacité des traitements actuels de la TB-MDR. Le premier objectif de cette thèse a été de caractériser un nouveau vaccin thérapeutique, basé sur le virus de la vaccine modifié d’Ankara (Modified Vaccinia virus Ankara, MVA), le MVATG18598, qui exprime dix antigènes représentatifs des trois phases de l’infection par Mtb. En utilisant différentes lignées de souris, nous avons montré que la vaccination par MVATG18598 entraîne l'induction de réponses spécifiques cellulaires et humorales. Les cellules T produisent plusieurs cytokines de type Th1 et présentent une activité cytolytique. Dans des modèles murins d’efficacité, le MVATG18598, associé à un traitement antibiotique, réduit significativement la charge bactérienne dans les animaux infectés ainsi que le taux de rechute de la maladie après l’arrêt du traitement. Le deuxième objectif de cette thèse a été d'analyser l'impact des antituberculeux sur l'immunogénicité du vaccin MVATG18598. Nous avons montré que les antibiotiques de première ligne, et principalement l’isoniazide, diminuent la réponse immunitaire Th1 induite par le MVATG18598. De plus, nous avons démontré que la réponse humorale induite par le candidat vaccin est modifiée et s’oriente vers une augmentation du rapport IgG1/IgG2a en présence d’antibiotiques. En conclusion, nous montrons qu'un vaccin immunothérapeutique, tel que le MVATG18598, a la capacité de contribuer au contrôle de la tuberculose en augmentant l'efficacité des traitements antituberculeux. De plus, nos résultats indiquent que les antibiotiques modulent la réponse immunitaire induite par le vaccin, données devant être prises en compte lors du développement des futures stratégies immunothérapeutiques / Tuberculosis (TB), a lung disease caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death worldwide from an infectious disease. TB is responsible for an estimated 1,7 million of deaths and 10,4 million new cases annually. The emergence and spreading of multidrug resistance (MDR) Mtb strains represent a major global threat and reflect limitation of current treatments. Patients with MDR-TB are currently treated with multiple drug regimens, often toxic, given for long durations, with a limited efficacy. Therefore, developing novel TB therapies is urgently needed. Immunotherapy aiming at triggering specific immune response against Mtb represents an attractive approach to shorten the duration and increase the efficacy of current MDR-TB treatment. The first aim of this PhD project was to characterize a novel therapeutic vaccine, based on the Modified Vaccinia virus Ankara (MVA), MVATG18598, expressing ten antigens representative of the three phases of Mtb infection. Using different strains of mouse, we showed that MVATG18598 vaccination is able to trigger Mtb antigens-specific humoral and cellular responses. Both CD4 and CD8 T cells display the capacity to produce multiple Th1-cytokines together with cytolytic activity. In post-exposure mouse models, MVATG18598 combined with an antibiotic regimen decreases significantly the bacterial burden in lungs of infected mice as well as the disease relapse rate after treatment completion. The second aim of this project was to analyze the impact of TB antibiotics on the immunogenicity of the MVATG18598 vaccine. We showed that first-line antibiotic regimen, mostly isoniazid, decreases antigen-specific Th1 immune response triggered by MVATG18598 vaccination in mice. Moreover, we demonstrated that Mtb-specific antibody response induced by the vaccine candidate is modified and shifted towards an increase of IgG1/IgG2a ratio in presence of drugs. Altogether, these results illustrate that immunotherapeutic vaccine such as MVATG18598 has the capacity to contribute to the control of TB by improving efficiency of anti-TB drugs treatment. In addition, our results indicate that antibiotics are able to modulate vaccine-induced immune response, a feature to consider for the future development of immunotherapies

Streptococcus pneumoniae est une bactérie cocci gram positif commensale de la flore oropharyngée qui colonise le rhinopharynx de l’Homme et dont près de 100 sérotypes sont connus. Les nourrissons et les jeunes enfants représentent son réservoir principal. Le pneumocoque peut être à l’origine d’infections graves, telles que la méningite, les bactériémies et la pneumonie, et moins graves mais plus courantes comme la sinusite et l’otite moyenne aiguë. Deux vaccins anti-pneumococciques conjugués ont été introduits en France : le PCV7 (couvrant contre 7 sérotypes) en 2003 et le PCV13 (couvrant contre 6 sérotypes supplémentaires) en 2010. L’objectif général de ce travail de thèse est d’évaluer l’impact des politiques vaccinales sur les infections invasives à pneumocoque en France, en s’intéressant principalement aux évolutions temporelles et géographiques des plus graves : les méningites à pneumocoque (MP). Un premier travail a étudié les dynamiques temporelles des MP sur la période 2001–2014 afin d’identifier l’impact de l’introduction des vaccins conjugués. Des techniques statistiques de modélisations adaptées aux séries temporelles ont été utilisées. Les résultats de ce travail retrouvent des effets rapportés dans la littérature : une réduction des MP à sérotypes vaccinaux mais aussi une augmentation des MP dues aux sérotypes non inclus dans le vaccin (phénomène de « remplacement sérotypique »).Par conséquent, le premier bénéfice, à l’échelle de la population générale, de l’introduction de cette vaccination a été observé seulement onze ans après l’introduction du PCV7, et principalement suite à l’introduction du PCV13 en 2010, avec une diminution de 25% du nombre de MP en 2014. La composante géographique a ensuite été prise en compte afin d’étudier le rôle de la de couverture vaccinale dans la variabilité des MP annuelles entre les départements sur la période 2001-2016. Les résultats confirment l’efficacité des deux formulations du vaccin sur les MP dues aux sérotypes vaccinaux et suggèrent une certaine homogénéité de cet effet entre les différents départements. Inversement, le remplacement sérotypique a été confirmé mais uniquement suite à l’introduction de la première formulation du vaccin et ces effets présentent une répartition géographique hétérogène et variable. La variabilité de la couverture vaccinale entre les départements n’explique pas celle observée dans le nombre de MP, ce qui suggère l’intervention d’autres facteurs tel que la densité géographique. Enfin, une modélisation dynamique, permettant de prendre en compte des aspects fondamentaux des dynamiques de transmission et d’infection du pneumocoque non intégrés dans les méthodes de modélisation statique, a été proposée afin de prédire l’impact de différentes stratégies de vaccination pour les adultes de 65 ans et plus et ainsi évaluer leur rapport coût-utilité. / Streptococcus pneumoniae is a Gram-positive commensal bacterium of the oropharyngeal flora usually colonizing human’s rhino pharynx, of which almost 100 serotypes are known. Infants and young children constitute its main reservoir. Pneumococcus may cause serious infections, such as meningitis, bacteremia and pneumonia, or less serious but more common such as sinusitis and acute otitis media (AOM). Two conjugate pneumococcal vaccines have been introduced in France: PCV7 (covering 7 serotypes) in 2003 and PCV13 (covering 6 additional serotypes) in 2010. The overall objective of this thesis is to assess the impact of vaccination policy on invasive pneumococcal diseases in France, by focusing on temporal and geographical trends of the most serious of them: pneumococcal meningitis (PM). An initial study of PMs temporal dynamics over the 2011-2014 period assessed the impact of conjugate vaccines’ introduction. Statistical modeling techniques were used for time series analysis. The results confirm the effects found in literature: a reduction of vaccine serotypes PMs but at the same time an increase of PMs, due to non-vaccine serotypes (effect of “serotype replacement”). Therefore, the first benefit of vaccine introduction at population scale has been observed no less than 11 years after PCV7 introduction, and then principally after PCV13 was introduced in 2010, with a 25% decrease in PMs in 2014. The geographic component was then implemented to analyze the role of vaccine coverage in annual PM variability between geographic units over the 2001-2016 period. Results confirm the effectiveness of both vaccine compositions on vaccine serotypes PMs and suggest homogeneity of this effect among geographic units. Conversely the serotype replacement has been confirmed only after the first vaccine composition was introduced and presents a variable and heterogeneous geographical repartition. Variability in vaccine coverage among geographic units doesn’t explain the differences in PMs, which could suggest the role of others factors such as demographic density. Finally, a dynamic modeling capable of taking into consideration fundamental aspects of pneumococcus transmission and infection mechanisms not integrated in static modeling has been proposed in order to predict the impacts of different vaccination strategies for 65+ adults and therefore assess their cost-utility ratios.

Introduktion: Kolera är en sjukdom som orsakar akut diarré. Kolera fortsätter att orsaka stor sjukdomsbörda och dödlighet världen över. Vaccin mot kolera kan användas i kombination med WASH åtgärder (wash, sanitation and hygiene) för att stävja utbrott eller som proaktiv åtgärd i områden som anses vara högriskområden för att drabbas av kolera. Trots att WHO (Världshälsorganisationen) sedan 2010 rekommenderar vaccin som en reaktiv åtgärd vid utbrott används det sällan på grund av en global brist av vaccin och bristen på forskning kring vaccinets effekt i verkliga miljöer, särskilt vid pågående kolera utbrott. Det finns fortsatt ett behov att utforska vaccin som en reaktiv åtgärd vid pågående kolera utbrott. Syfte: Syftet med studien var att analysera effekten av vaccin vid pågående kolera utbrott. Metod: En systematisk litteraturöversikt där analysen utfördes genom narrativ syntes. Även en evidensgradering enligt EPPI-center modellen utfördes. Resultat: Resultatet av syntesen antyder att vaccin kan vara effektivt som en reaktiv åtgärd, även i miljöer där befolkningen saknar grundläggande immunitet. Två doser vaccin ger ett skydd som varar i upp till fyra år, effekten av vaccinet varierar inte nämndvärt beroende på hur lång tid som passerat sedan vaccinering. Effekten av vaccinet är högre i endemiska miljöer, skillnaden är dock marginell.Slutsats: Vaccin kan vara en effektiv åtgärd för att kontrollera utbrott av kolera. / Introduction: Cholera is an acute diarrhoeal disease with high morbidity and mortality globally. Oral cholera vaccines can be used in conjunction with improvements of water and sanitation to control cholera outbreaks as well as for prevention in areas known to be in high risk for cholera. Altough WHO has recommended oral cholera vaccines as a reactive measure since 2010 they are not routinely used during cholera outbreaks due to global vaccine shortage and the scarcity of data on the effectiveness of the vaccines in real life settings, especially during a cholera epidemic. As a consequense of this there is a need to explore the effectiveness of reactive use of oral cholera vaccines during cholera outbreaks. Aim: The aim of this study was to analyze the effectiveness of oral cholera vaccines in response to an outbreak. Method: Astructured literature review was performed and analysed trough narrative synthesis. Furthermore an assesment of the overal weight of evidence was conducted using the EPPIaproach. Result: The result of the synthesis suggest that vaccines may be an effective reactive measure during an outbreak, even in areas of little or no recent exposure to cholera. Two doses of oral cholera vaccine provides protection, lasting up to four years. The effectiveness did not wary much depending on the time passed since vaccination. The vaccine effectiveness is higher in endemic settings, altough the difference is only marginal. Conclusion: The findings suggest that vaccine may be effective in controlling cholera outbreaks.

Streptococcus suis est une bactérie pathogène qui cause d'importantes pertes économiques dans l'industrie porcine à travers le monde. Comme il n’existe pas de vaccins commerciaux en Amérique du Nord, l'utilisation d'autovaccins administrés aux cochettes/truies pour induire des anticorps passifs chez les porcelets représente une alternative intéressante pour les producteurs. Cependant, il n’existe aucune production standardisée de ces vaccins et le produit final peut être très différent d'un laboratoire agréé à l'autre. Dans la présente étude, un vaccin autogène (« bacterin ») polyvalent contenant les sérotypes 1/2, 2, 5, 7 et 14 de S. suis a été préparé par un laboratoire agréé et utilisé dans un programme de trois doses administrées aux cochettes par voie intramusculaire. La réponse humorale (anticorps) chez les cochettes ainsi que le transfert passif d'anticorps aux porcelets ont été évalués. Contrairement à ce qui avait été publié précédemment avec un vaccin autogène produit par une autre compagnie, la réponse anticorps accrue observée chez les cochettes vaccinées était suffisante pour améliorer le transfert d'anticorps maternels aux porcelets âgés de 3 à 5 semaines. Cependant, les porcelets resteraient encore sensibles à la maladie à S. suis qui apparaît souvent pendant la deuxième partie de la période en pouponnière. Le niveau élevé d'anticorps n'a pas affecté l'excrétion de S. suis (ainsi que celle de sérotypes spécifiques de S. suis inclus dans le vaccin) chez les cochettes et les porcelets. Bien que tous les traitements antibiotiques aient été absents pendant l'essai, l'effet protecteur clinique du programme de vaccination avec le vaccin autogène n'a pas pu être évalué, car des cas limités d’infection à S. suis étaient présents pendant l'essai. D'autres essais pour évaluer l'utilité de la vaccination des cochettes/truies avec des vaccins autogènes pour protéger les porcelets de pouponnière devraient être réalisés. Il est nécessaire, pour les futurs essais sur le terrain, de toujours inclure un groupe témoin non vacciné, d'éliminer si possible tout traitement antimicrobien dans l'élevage et de confirmer l'étiologie des cas cliniques par un diagnostic en laboratoire lors de l'évaluation de l'effet protecteur de tels vaccins autogènes. / Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no commercial vaccines available in North America, the use of autogenous vaccines applied to gilts/sows to induce maternal antibodies to protect piglets is an attractive alternative for producers. However, there is no universal standardization in the production of such vaccines and the final product may be highly different among licenced laboratories. In the present study, a polyvalent autogenous vaccine (“bacterin”) with S. suis serotypes 1/2, 2, 5, 7 and 14 was prepared by a licenced laboratory and used in a three-dose program given to gilts intramuscularily. The humoral (antibody) response in gilts as well as the passive transfer of antibodies to piglets were evaluated. Different from what was previously published with an autogenous vaccine produced by a different company, the increased response seen in vaccinated gilts when compared to non-vaccinated animals was sufficient to improve maternal antibody transfer to piglets of 3 to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease that often appears during the second part of the nursery period. The high level of antibodies did not affect S. suis (as well as that of specific serotypes of S. suis included in the vaccine) shedding by both, gilts and piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis clinical cases were present during the trial. Further trials to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done. There is a need, for future field trials, to always include a control non-vaccinated group, to eliminate if possible any antimicrobial treatment in the farm and to confirm the etiology of clinical cases by a diagnostic laboratory when evaluating the protective effect of such autogenous vaccines.

La prévalence de Streptococcus suis, notamment du sérotype 2, à l’échelle mondiale pose de grands problèmes à l’industrie porcine ainsi qu’à la santé publique. La compréhension des mécanismes immunitaires permettant alors de lutter contre cette bactérie devient un atout majeur dans le développement des vaccins. S. suis dispose cependant d’un puissant arsenal pour contrer ces mécanismes. Enveloppé d’une capsule polysaccharidique (CPS), cette bactérie résiste à la phagocytose, à moins que certaines cellules soient en mesure de produire des anticorps opsonisants. Par chance, au sein de la rate, en périphérie du follicule, une zone nommée la « zone marginale » regroupe des lymphocytes B spécialisés dans la réponse aux bactéries encapsulées et aux antigènes polysaccharidiques. Ceci sans l’intervention des lymphocytes T auxiliaires, contrairement aux lymphocytes B se trouvant à l’intérieur du follicule, qui interviennent dans une réponse plus dirigée contre des antigènes protéiques. L’objectif général de ce mémoire est donc l’étude de la réponse anticorps dite « extrafolliculaire » que les LB-MZ sont suspectés d’orchestrer lors d’une infection à S. suis. En premier lieu nous avons déterminé la cinétique de différentiation en plasmocytes des LB-MZ (LB-MZ) lors de l’infection par S. suis. Puis nous avons étudié la fonctionnalité et le type d’anticorps produits par ces LB-MZ. Les présents travaux ont démontré toute l’importance des LB-MZ dans l’élimination de la bactérie ou dans le ralentissement de sa dissémination systémique durant les premiers stades de l’infection, notamment grâce à un environnement propice à la différenciation en plasmocytes. Les principaux anticorps produits à cet effet étaient de classe IgM et dirigés contre des antigènes de la CPS. Nos résultats éclairent un peu plus la voie, et permettent d’imaginer des options pour le développement des vaccins qui activeraient spécifiquement cette réponse extrafolliculaire efficace. / The worldwide prevalence of Streptococcus suis, particularly serotype 2, poses major problems for the pig industry and public health. Understanding the immune mechanisms involved in combating this bacterium is becoming a major asset in the development of vaccines. However, S. suis has a powerful arsenal at its disposal to counter these mechanisms. Enveloped in a polysaccharide capsule (CPS), this bacterium resists phagocytosis unless certain cells can produce opsonising antibodies. Fortunately, within the spleen, at the periphery of the follicle, a zone known as the "marginal zone" contains B lymphocytes specialised in responding to encapsulated bacteria and polysaccharide antigens. This is without the intervention of T helper lymphocytes, unlike the B lymphocytes inside the follicle, which are involved in a response more directed against protein antigens. The general objective of this thesis is therefore to study the so-called 'extrafollicular' antibody response that LB-MZ are thought to orchestrate during S. suis infection. We first determined the kinetics of LB-MZ differentiation into plasma cells during S. suis infection. We then studied the functionality and type of antibodies produced by these LB-MZs. This work has demonstrated the importance of LB-MZ in eliminating the bacterium or slowing down its systemic dissemination during the early stages of infection, thanks to an environment conducive to differentiation into plasma cells. The main antibodies produced for this purpose were IgM class antibodies directed against CPS antigens. Our results shed a little more light on the pathway, and allow us to imagine options for the development of vaccines that would specifically activate this effective extrafollicular response.

L'efficacité de la réponse antitumorale repose sur l'activité des cellules T cytotoxiques, qui peut être stimulée par des vaccins contenant des antigènes spécifiques aux tumeurs. Malgré le fait d'être les principales cellules présentatrices d'antigènes (CPA) responsables de l'activation des cellules TCD8, les cellules dendritiques (CD) ont rencontré des défis dans le développement de vaccins contre le cancer, notamment en ce qui concerne leur fabrication et efficacité. Pour combler ces problèmes, cette étude propose d’utiliser des cellules stromales mésenchymateuses (CSM) comme plateforme de vaccination alternative, en exploitant les avantages des CSMs en matière de fabrication, de sécurité et de plasticité. La plasticité remarquable des CSMs leur permet d'acquérir une capacité de présentation croisée sous des stimuli spécifiques. Étant donné que la présentation croisée est essentielle pour induire l'activation des cellules T contre les antigènes tumoraux, cette étude vise à convertir les CSMs en cellules présentatrice d‘antigènes en améliorant l'exportation des antigènes des endosomes vers le cytosol - une étape critique du processus. Dans cette démarche, nous avons examiné une librairie de molécules dérivés de l’Accum, une molécule initialement conçue pour favoriser la destruction de la membrane endosomale. Après avoir évalué leur potentiel à induire la présentation croisée, nous avons sélectionné la molécule A1 pour des investigations subséquentes. Les études mécanistiques ont démontré qu'A1 déclenchait des processus cellulaires essentiels favorisant une présentation croisée efficace, notamment une augmentation de la capture, dégradation et évasion des antigènes des endosomes ainsi que la production de d’espèces oxygénés réactifs. L'efficacité thérapeutique des CSMs reprogrammées par A1 (ARM) en tant que vaccin anticancéreux a été évaluée chez des souris ayant des tumeurs, en monothérapie et en combinaison avec l’anti-PD-1. La thérapie combinée ARM a induit une régression tumorale et a augmenté les taux de survie dans les modèles de tumeurs solides. En conclusion, cette étude présente une stratégie innovante pour transformer les CSM en cellules à présentation croisée en déclenchant l'échappement endosomal de l'antigène. Les cellules ARMs en association avec des inhibiteurs des points de contrôle immunitaire présentent un potentiel en tant que plateforme de vaccination contre les tumeurs solides. De plus, ces résultats soulignent l'importance de l'évasion des endosomes dans la présentation croisée d‘antigènes et ouvrent la voie à de nouvelles plateformes de vaccins contre le cancer. / The effectiveness of antitumoral response relies on cytotoxic T-cell activity, which can be stimulated through vaccines carrying tumor-specific antigens. Despite being the primary antigen-presenting cells (APCs) responsible for CD8 T-cell activation, dendritic cells (DCs) have encountered challenges in cancer vaccine development, particularly in manufacturing and efficiency. To address this gap, this study proposes mesenchymal stromal cells (MSCs) as an alternative vaccine platform, leveraging the advantages in manufacturing, safety profile, and plasticity of MSCs. The remarkable plasticity of MSCs enables them to acquire cross-presentation capacity under specific stimuli. Given that cross-presentation is pivotal for inducing T-cell activation against tumor antigens, this study aims to convert MSCs into antigen cross-presenting cells by enhancing the export of antigens from endosomes to the cytosol—a critical step in the process. In this pursuit, we screened a library of Accum and variant molecules designed to promote endosomal disruption. After evaluating their potential to induce cross-presentation, we selected the molecule A1 for further investigation. Mechanistic studies demonstrated that A1 triggers essential cellular processes supporting efficient cross-presentation, including enhanced antigen uptake, processing, endosomal escape, and reactive oxygen species production. The therapeutic efficacy of A1-reprogrammed MSCs (ARMs) as an anticancer vaccine was evaluated in tumor-bearing mice, as monotherapy and combined with anti-PD-1. In solid tumor models, ARMs combination therapy induced tumor regression and increased survival rates. In conclusion, this study presents an innovative strategy to transform MSCs into cross-presenting cells by triggering antigen endosomal escape. ARM cells in combination with immune checkpoint inhibitors hold potential as a vaccination platform against solid tumors. These findings underscore the importance of endosomal escape on antigen cross-presentation and pave the way for new cancer vaccine platforms.

I december 2019 rapporterades ett utbrott av lunginflammation i Wuhan, Kina. 7 januari 2020 identifierades det då nya coronaviruset, virusets spreds och 11 mars 2020 klassades covid-19 som en pandemi av världshälsoorganisationen (WHO). Covid-19-pandemin har föranlett stor negativ inverkan på folkhälsan, samhället liksom ekonomin världen över. Sedan upptäckten av viruset har flera osäkerheter följt vilket kommit att känneteckna covid-19-pandemin. Osäkerheter har resulterat i flertalet hanteringsåtgärder, men sedan vaccinets introduktion är det den primära hanteringsstrategin. 29 januari 2021 godkände EU vaccinet från Oxford-Astra Zeneca och fram till 9 april 2021 administrerades ca 17 miljoner doser av Oxford-Astra Zeneca-vaccinet. 7 april 2021 meddelade dock europeiska läkemedelsmyndigheten (EMA) att det finns en koppling mellan vaccinet och risken för trombos i kombination med trombocytopeni (TTS)/vaccininducerad immuntrombotisk trombocytopeni (VITT) (båda avser risk för blodpropp). Symptom som kan uppkomma är bl.a. andnöd, bröstsmärtor och huvudvärk. Det kan även leda till död. Detta är en mycket sällsynt biverkning och EMA förklarar att de övergripande fördelarna med vaccinet överväger riskerna för biverkningar. Studien syftar till att undersöka hur risken med Oxford-Astra Zeneca-vaccinet har hanterats av olika Europeiska länder liksom hur motivet till beslutet formulerats och kommunicerats. Tidigare studier visar att riskkommunikationen påverkar individers vilja att ta vaccin, men ingen studie omfattar kopplingen mellan länders beslut och efterföljande riskkommunikation. Följande frågor besvaras i studien: (1) Vilket beslut har länderna tagit gällande administrationen av Oxford-Astra Zeneca-vaccinet? (2) Hur motiverar olika länder sitt beslut? Vilka beslutsunderlag har betonats? (3) Kan mönster eller tendenser urskiljas vad gäller beslutet och efterföljande riskkommunikation? I så fall vilka mönster eller tendenser kan urskiljas? För att besvara frågorna har en kartläggning av ländernas beslut gjorts som ett första steg. I det andra steget har riskmeddelanden från regeringar till medborgare analyserats med hjälp av 14 frågor som konstruerats utifrån teorin kring riskkommunikation. Detta bygger på riskkommunikationsprocessen liksom mål och strategier inom riskkommunikation. Målet med kommunikationen kan vara allt från att informera till att försöka skapa beteendeförändring. Riskkommunikationsprocessen innebär inflytande från olika aktörer där makt, vetenskap samt politik blir aktuellt. Betydelsen av transparens i riskkommunikation samt öppenhet kring osäkerhet påpekas i flera tidigare studier och utgör en del av diskussionen. Resultatet visar att länder har tagit olika beslut. Fyra beslutskategorier har identifierats: (1) Länder som accepterar risken för biverkning och ger AZ till samtliga medborgare. (2) Länder som delvis accepterar risken för biverkning och infört en åldersgräns för att begränsa risken. (3) Länder som överfört beslutet och ansvar kring risken till medborgarna genom att behålla vaccinet i landet och administrerar AZ-vaccinet till frivilliga. (4) Länder som inte accepterar risken för biverkning och därmed slutar att administrera AZ. Mönster har identifierats t.ex. att länder som ställer sig positiva till Oxford-Astra Zeneca-vaccinet också kommunicerar positiv information kring vaccinet till medborgarna. I länder där medborgare själva får besluta om vaccinet kan ytterligare belastning på sjukvården ges då flera av dessa länder beslutat att hälso- och sjukvård ska hjälpa individen i dennes beslut kring vaccinet. Detta förekommer inte i någon annan beslutskategori. Osäkerhet har fått varierande tyngd i ländernas beslut och kommunikationen kring osäkerhet varierar. Även om det finns osäkerheter kommuniceras dessa inte alltid. Beslutet får konsekvenser och är därmed mer än bara ett beslut om risk. / In December 2019, an outbreak of pneumonia was reported in Wuhan, China. The new coronavirus was identified on January 7, 2020. The virus spread and on March 11, 2020, covid-19 was classified as a pandemic by the World Health Organization (WHO). The Covid-19 pandemic has caused a major negative impact on public health, society as well as the economy worldwide. Since the discovery of the virus, several uncertainties have followed. These uncertainties characterize the covid-19 pandemic. Different management measures have been implemented. Since the vaccine got introduced, vaccination has been the primary management strategy. On January 29, 2021, the EU approved the Oxford-Astra Zeneca vaccine and until April 9, 2021, approximately 17 million doses of the Oxford-Astra Zeneca vaccine have been administered. However, on April 7, 2021, the European Medicines Agency (EMA) announced a link between this vaccine and the risk of thrombosis in combination with thrombocytopenia (TTS)/vaccine-induced immune thrombotic thrombocytopenia (VITT) (both refer to the risk of blood clots).. Blood clots can lead to breathing difficulties, chest pain, headache, and death. Blood clots are very rare and the EMA explains that the overall benefits of the vaccine outweigh the risks. The study aims to investigate how the risk connected to the Oxford-Astra Zeneca vaccine has been handled by various European countries as well as how they motive and communicate their decisions. Previous studies show that risk communication influence on individuals' willingness to take vaccines, but no study covers the link between countries' decisions and risk communication. The following questions are answered in the study: (1) What decision has each country made regarding the administration of the Oxford-Astra Zeneca vaccine? (2) How do these countries justify their decision? On which bases have the countries made their respective decisions? (3) Can patterns or tendencies be discerned regarding the decision and subsequent risk communication? If so, what patterns or tendencies can be discerned? In order to answer these questions, the countries' decisions have been mapped, as a first step. The second step has been to analyze risk messages from governments to citizens using 14 questions based on risk communication theory. These questions are based on the risk communication process as well as objectives and strategies within risk communication. The goal of the communication varies from informing the receiver to create behavioral change. Risk processes involve debates between various actors where power, science and politics become relevant. The importance of transparency in risk communication and openness around uncertainty is pointed out in several previous studies. The result shows that countries have taken different decisions. Four categories of decisions have been identified: (1) Countries that accept the risk of side effects and provide AZ to all citizens. (2) Countries that partially accept the risk of side effects and introduced an age limit to limit the risk. (3) Countries that transferred the decision and responsibility to the citizens by keeping the vaccine in the country and administering the AZ vaccine to volunteers. (4) Countries that do not accept the risk of side effects and thus stop administering AZ. Patterns have been identified, for example countries whit a positive attitude to the Oxford-Astra Zeneca vaccine communicate positive information about the vaccine to citizens. In several countries, where the citizens decide vaccine, the countries have decided that the healthcare system should help the individual in the decision regarding the vaccine. This can result in an additional burden on the healthcare system. Several of these countries have decided that the healthcare system should help the individual in the decision regarding the vaccine. This does not occur in any other decision category. Uncertainty has been given varying weight in the countries' decisions and communication around uncertainty varies. Even if there are uncertainties, these are not always communicated. The decision has consequences and it is just more than a decision about risk.

In times of crises such as pandemics, wars or natural disasters, the responsibility of the news media increases. Previous research has shown that people in crisis tend to seek information in traditional media and find it the most reliable source. Today's media landscape has faced a new paradigm shift in the form of digitalization that has had an extensive impact on society and information is now more easily available to the public. As a result, this study will examine the ongoing COVID-19 pandemic with a focus on vaccination, which has received strong media attention in Sweden. The purpose of this study is to contribute with new research by analyzing how Sweden's largest morning newspaper Dagens Nyheter and the largest evening newspaper Aftonbladet communicated regarding the COVID-19 vaccine. The study's four research questions aim to investigate whether there are any differences or similarities in how Aftonbladet and Dagens Nyheter communicated through source power, tabloidization, and dimensions from previous research: RQ1. How does Aftonbladet and Dagens Nyheter use and mention sources in their articles RQ2. How are the articles conducted in Aftonbladet and Dagens Nyheter regarding focus dimensions (societal or individual, episodic or thematic)? RQ3. How are the articles conducted in Aftonbladet and Dagens Nyheter regarding style dimensions (personal or impersonal, emotional or unemotional)? RQ4. Do the articles in Aftonbladet and Dagens Nyheter have tendencies of tabloidization based on the content and headline (positive or negative, match between headline and text)? To answer the four research questions, a quantitative content analysis has been used by analyzing a total of 200 newspaper articles over a six-month period. With assistance of the tool Retriever, 100 articles from each newspaper were retrieved and produced through an unbound random selection. With help of the designed code sheet and the code book the units have been analyzed in SPSS. The theoretical framework is based on the basic principles of journalism, from event to news, agenda-setting, framing, and tabloidization. The data have been analyzed, reflected and discussed with the theoretical framework along with the previous research, the results show that Swedish media has shown a high scale of objectivity however, tendencies of tabloid permeate in both newspapers. The most important finding of the study is the indication that Dagens Nyheter, which according to previous research tends to cover hard news, instead strive against further tabloidized news coverage. / I tider av kriser så som pandemier, krig eller naturkatastrofer ökar nyhetsmedias ansvar. Tidigare forskning har visat att människor i kris tenderar att söka efter information i traditionella medier för att hitta den mest pålitliga källan. Dessutom har dagens medielandskap stött på ett nytt paradigmskifte i form av digitalisering som har haft en vidsträckt påverkan på samhället och information är nu lättare tillgänglig för allmänheten. Som ett resultat kommer denna studie att undersöka den pågående COVID-19-pandemin med fokus på vaccination, som har fått mycket uppmärksamhet i media. Syftet med denna studie är att bidra med ny forskning genom att analysera hur Sveriges största morgontidning Dagens Nyheter och den största kvällstidningen Aftonbladet kommunicerat angående COVID-19-vaccinet. Studiens fyra forskningsfrågor syftar till att undersöka om det finns några skillnader eller likheter i hur Aftonbladet och Dagens Nyheter kommunicerat genom källkraft, tabloidisering och dimensioner från tidigare forskning: RQ1. Hur använder och nämner Aftonbladet och Dagens Nyheter källor i sina artiklar? RQ2. Hur är artiklarna i Aftonbladet och Dagens Nyheter utformade gällande fokusdimensioner (samhällelig eller individuell, episodisk eller tematisk)? RQ3. Hur är artiklarna i Aftonbladet och Dagens Nyheter utformade gällande stildimensioner (personlig eller opersonlig, känslomässig eller okänslomässig)? RQ4. Har artiklarna i Aftonbladet och Dagens Nyheter tendenser till tabloidisering baserat på innehåll och rubrik (positiv eller negativ, matchning mellan rubrik och text)? För att svara på de fyra frågorna har en kvantitativ innehållsanalys använts genom att analysera totalt 200 tidningsartiklar under en sexmånadersperiod. Med hjälp av verktyget Retriever har 100 artiklar från varje tidning valts ut genom ett obundet slumpmässigt urval. Med hjälp av det utformade kodschemat och kodboken har enheterna analyserats i SPSS. Det teoretiska ramverket bygger på journalistikens grundläggande principer, från händelse till nyheter, agenda-setting, framing och tabloidisering. Datan har analyserats, reflekteras och diskuteras med hjälp av teoretiska ramen samt tidigare forskning. Resultaten visar att de svenska medierna har kommunicerat med en hög grad av objektivitet, men att tabloidiseringen genomsyrar båda tidningar. Studiens viktigaste resultat visar bland annat att Dagens Nyheter, som enligt tidigare forskning tenderar att rapportera hårda nyheter, istället lutar mot en mer tabloidisering i sin nyhetsrapportering.