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Articles de revues sur le sujet "Anti-cytokines vaccination"
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Agrati, Chiara, Concetta Castilletti, Delia Goletti, Silvia Meschi, Alessandra Sacchi, Giulia Matusali, Veronica Bordoni et al. « Coordinate Induction of Humoral and Spike Specific T-Cell Response in a Cohort of Italian Health Care Workers Receiving BNT162b2 mRNA Vaccine ». Microorganisms 9, no 6 (16 juin 2021) : 1315. http://dx.doi.org/10.3390/microorganisms9061315.
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Vaccination is the main public health measure to reduce SARS-CoV-2 transmission and hospitalization, and a massive worldwide scientific effort resulted in the rapid development of effective vaccines. This work aimed to define the dynamics of humoral and cell-mediated immune response in a cohort of health care workers (HCWs) who received a two-dose BNT162b2-mRNA vaccination. The serological response was evaluated by quantifying the anti-RBD and neutralizing antibodies. The cell-mediated response was performed by a whole blood test quantifying Th1 cytokines (IFN-γ, TNF-α, IL-2), produced in response to spike peptides. The BNT162b2-mRNA vaccine induced both humoral and cell-mediated immune responses against spike peptides in virtually all HCWs without previous SARS-CoV-2 infection, with a moderate inverse relation with age in the anti-RBD response. Spike-specific T cells produced several Th1 cytokines (IFN-γ, TNF-α, and IL-2), which correlated with the specific-serological response. Overall, our study describes the ability of the BNT162b2 mRNA vaccine to elicit a coordinated neutralizing humoral and spike-specific T cell response in HCWs. Assessing the dynamics of these parameters by an easy immune monitoring protocol can allow for the evaluation of the persistence of the vaccine response in order to define the optimal vaccination strategy.
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Ramakrishnan, Amritha, Keri Altoff, Andrew Pekosz et Jay Bream. « Immune Response to Seasonal Influenza Vaccination (92.18) ». Journal of Immunology 184, no 1_Supplement (1 avril 2010) : 92.18. http://dx.doi.org/10.4049/jimmunol.184.supp.92.18.
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Abstract The emergence of new pandemic strains of influenza highlights the need to better understand the immune response to vaccination in order to develop novel vaccine strategies. The goal of our study was to identify and assess novel markers of immune activation after vaccination. To this end, 100 healthy adults who received either the seasonal Live Attenuated Vaccine (LAIV) or the Inactivated Vaccine (TIV) were enrolled from 2006-2008. First, we measured the serum antibody titers against vaccine strains of the virus. We found that while TIV induced a robust increase in anti-influenza serum antibody titers, LAIV induced only a modest increase. We next measured the levels of 10 cytokines in the serum of vaccine recipients. Vaccination with TIV resulted in a significant reduction in the levels of TNF-α while LAIV had no effect on any of the measured cytokines. Finally, we assessed the ability of seasonal vaccination to induce neutralizing antibody titers against the pandemic 2009 H1N1 strain. Vaccination with TIV was able to induce a significant increase in cross reactive antibodies against different seasonal H1N1 strains but not against the 2009 pandemic H1N1 strain. In all, these data suggest that 1) different influenza A vaccine formulations induce unique cytokine responses in the periphery and 2) seasonal influenza vaccination does not illicit strong cross-reactive serum antibodies with 2009 H1N1.
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Shen, Chih-Lung, Tso-Fu Wang, Chao-Zong Liu et Yi-Feng Wu. « Platelet Activation and Cytokine Release of Interleukin-8 and Interferon-Gamma-Induced Protein 10 after ChAdOx1 nCoV-19 Coronavirus Vaccine Injection ». Vaccines 11, no 2 (16 février 2023) : 456. http://dx.doi.org/10.3390/vaccines11020456.
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Coronavirus disease 2019 (COVID-19) vaccines are associated with serious thromboembolic or thrombocytopenic events including vaccine-induced immune thrombocytopenia and thrombosis and immune thrombocytopenia, particularly AZD1222/ChAdOx1. According to the proposed mechanism, COVID-19 vaccines stimulate inflammation and platelet activation. In this study, we analyzed the role of AZD1222/ChAdOx1 vaccines in the activation of platelets and the release of anti-PF4 antibodies and inflammatory cytokines in a cohort of healthy donors without vaccine-induced immune thrombotic thrombocytopenia (VITT). Forty-eight healthy volunteers were enrolled in this study. Blood samples were collected from peripheral blood at three time points: before vaccination and 1 and 7 days after vaccination. Compared with the prevaccination data, a decrease in the leukocyte and platelet counts was observed 1 day after vaccination, which recovered 7 days after injection. The percentage of activated GPIIb/IIIa complex (PAC-1) under high ADP or thrombin receptor-activating peptide stimulation increased 1 day after vaccination. Furthermore, interluekin-8 (IL-8) and interferon-gamma-induced protein 10 (IP-10) increased significantly. Additionally, platelet activation and inflammation, with the release of cytokines, were observed; however, none of the individuals developed VITT. Mild thrombocytopenia with platelet activation and inflammation with an elevation of IL-8 and IP-10 were observed after AZ vaccination.
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Trofin, Felicia, Olivia Simona Dorneanu, Daniela Constantinescu, Eduard Vasile Nastase, Cătălina Luncă, Luminița Smaranda Iancu, Ioana-Maria Andrioaie et al. « Cytokines and Chemokines in Breastmilk of SARS-CoV-2 Infected or COVID-19 Vaccinated Mothers ». Vaccines 10, no 12 (24 novembre 2022) : 2001. http://dx.doi.org/10.3390/vaccines10122001.
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Introduction: The COVID-19 disease and anti-SARS-CoV-2 vaccination were accompanied by alterations in several inflammatory markers. The aim of our research was to check to what extent such cytokines are transferred to infants via the breastmilk of SARS-CoV-2-infected or vaccinated mothers. Thus, we wanted to check if breastfeeding is safe during SARS-CoV-2 infection or after COVID-19 mRNA-vaccination. Material and method: The Luminex Multiplexing Assay was used for quantifying 10 cytokine in the human breastmilk of SARS-CoV-2-infected or COVID-19-vaccinated mothers, compared with anti-SARS-CoV-2 IgG naïve mothers. Two milk samples were collected at 30 and 60 days either after the booster dose or afterthe onset of symptoms. A single milk sample was collected from the mothers within the control group. Results: The cytokine concentrations were mostly found within the reference intervals for all mothers. The status of the vaccinated/infected mother, the age of the breastfed child, the parity of the mother and the maternal age were variation factors of the above-mentioned cytokine concentrations. The type of birth and the presence of IgG in the milk had no influence on these cytokine concentrations in milk. Furthermore, no statistically significant differences were recorded between the cytokine concentrations of the two milk samples. Conclusion: Our study provides data that support the safety of breastfeeding in the case of mild COVID-19 infection or after Pfizer or Moderna vaccinations.
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Gazzinelli, R. T., F. T. Hakim, S. Hieny, G. M. Shearer et A. Sher. « Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. » Journal of Immunology 146, no 1 (1 janvier 1991) : 286–92. http://dx.doi.org/10.4049/jimmunol.146.1.286.
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Abstract BALB/c mice vaccinated with a temperature-sensitive mutant (TS-4) of Toxoplasma gondii develop complete resistance to lethal challenge with a highly virulent toxoplasma strain (RH). This immunity is known to be dependent on IFN-gamma synthesis. In vitro and in vivo T cell depletions were performed in order to identify the subsets responsible for both protective immunity and IFN-gamma production. When stimulated with crude tachyzoite Ag in vitro, CD4+ cells from vaccinated mice produced high levels of TH1 cytokines (IL-2 and IFN-gamma) but not TH2 cytokines (IL-4 and IL-5). CD8+ cells, in contrast, produced less IFN-gamma and no detectable IL-2. Nevertheless, they could be induced to synthesize IFN-gamma when exposed in culture to exogenous IL-2. In vivo treatment with anti-CD4 plus anti-CD8 or anti-IFN-gamma antibodies during challenge infection completely abrogated resistance to T. gondii. In contrast, treatment with anti-CD4 alone failed to reduce immunity, whereas anti-CD8 treatment partially decreased vaccine-induced resistance. These results suggest that although IFN-gamma and IL-2-producing CD4+ lymphocytes are induced by vaccination, IFN-gamma-producing CD8+ T cells are the major effectors of immunity in vivo. Nevertheless, CD4+ lymphocytes appear to play a synergistic role in vaccine-induced immunity, probably through the augmentation of IFN-gamma synthesis by the CD8+ effector cells. This hypothesis is supported by the observation that when giving during vaccination, as opposed to after challenge, anti-CD4 antibodies are capable of blocking protective immunity.
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Weir, Rosemary E., Gillian F. Black, Hazel M. Dockrell, Sian Floyd, Paul E. M. Fine, Steven D. Chaguluka, Sally Stenson et al. « Mycobacterial Purified Protein Derivatives Stimulate Innate Immunity : Malawians Show Enhanced Tumor Necrosis Factor Alpha, Interleukin-1β (IL-1β), and IL-10 Responses Compared to Those of Adolescents in the United Kingdom ». Infection and Immunity 72, no 3 (mars 2004) : 1807–11. http://dx.doi.org/10.1128/iai.72.3.1807-1811.2004.
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ABSTRACT To investigate the role of innate immunity in variable efficacy of Mycobacterium bovis BCG vaccination in Malawi and the United Kingdom, we examined 24-h tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-10 responses to mycobacterial purified protein derivatives (PPDs). The rank order in stimulatory potency for different PPDs was the same for all three cytokines. Before vaccination Malawians made higher pro- and anti-inflammatory responses than did United Kingdom subjects. Fewer than 5% of United Kingdom subjects made IL-10 in response to any PPD, compared to 19 to 57% responders among Malawians. Priming for regulatory IL-10 may contribute to the smaller increase in gamma interferon responses in Malawians compared to United Kingdom subjects following BCG vaccination.
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Khare, Priyanka, Saleem Javed, Swatantra Jain, Om Singh et Rahul Pal. « Potential roles of human chorionic gonadotropin in tumorigenesis and the development of novel vaccination strategies (P2116) ». Journal of Immunology 190, no 1_Supplement (1 mai 2013) : 132.48. http://dx.doi.org/10.4049/jimmunol.190.supp.132.48.
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Abstract Human chorionic gonadotropin (hCG) is associated with poor prognosis in several cancers, but causative molecular events remain inadequately described. In this study, tumor cells were found to express message for both hormonal subunits. Along with increasing cell viability, exogenous hCG enhanced several key tumor-promoting mechanisms. It induced the transcriptional activation and secretion of the angiogenic factors VEGF and IL8. Matrix-degrading enzymes associated with invasion (MMP2 and MMP9) were also enhanced, as was invasiveness. hCG up-modulated secretion of the proteoglycan versican and the consequent secretion of the inflammatory cytokines IL6 and TNFα from macrophages. hCG up-regulated FOXP3 in tumor cells, leading to the increased secretion of the immunosuppressive cytokines IL10 and TGFβ and up-modulation of CTLA-4; co-culture hCG-stimulated tumor cells with mature BMDCs heightened the secretion of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase. Anti-hCG antibodies restricted the growth of human tumor xenografts, and immunization with a novel anti-hCG vaccine formulation (βhCG-TT + Mycobacterium indicus pranii) synergistically attenuated tumor development and prolonged survival in syngeneic mice. By preventing autocrine and subsidiary paracrine hCG-induced effects on multiple pathways, new generation anti-hCG vaccines may therefore hold considerable promise as adjunct therapy in patients of gonadotropin-sensitive tumors.
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Ponikowska, Irena, Przemysław Adamczyk et Zbigniew Kupis. « Balneotherapy in Stimulating Resistance to Infections – the Little-used Health Resort’s Potential During the COVID-19 Pandemic ». Acta Balneologica 64, no 3 (2021) : 264–68. http://dx.doi.org/10.36740/abal202203111.
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To function properly, the human immune system must be adequately stimulated. Immune activity is stimulated as a result of the use of vaccines as well as the exposure of the body to infections. This type of stimulation only increases the specific humoral immunity, characterized by relatively short duration, and targeted at a well-defined antigen. In the case of the COVID-19 virus, immune memory cells persist for up to one year. In parallel with specific stimulation, it is necessary to develop non-specific immunity. It is the body’s first line of defense against infection, affects many microorganisms, and supports specific immunity. We can develop and strengthen this immunity using non-pharmacological methods, including balneotherapy, physical activity, and an appropriate diet. There is now much scientific evidence showing the effectiveness of balneotherapy in improving innate immunity. In in vitro and in vivo studies with high scientific credibility, the following effects of balneotherapy on the immune system were demonstrated: stimulation of the proliferation of T lymphocytes (especially CD4), normalization of the ratio between lymphocytes with different cytotoxic and anti-inflammatory effects, increased number of granulocytes and stimulation of the phagocytic activity of granulocytes and macrophages, lowering the concentration of proinflammatory cytokines and stimulating the secretion of anti-inflammatory cytokines, CRP, prostaglandins (PGE2), as well as antioxidant and neurohormonal activity. Among treatments with balneoimmunostimulatory effects, one should mention sulfide baths, peloid compresses, brine baths, radon treatments, and hot baths. These treatments are mainly used as part of health resort treatment. In Poland, health resort treatment represents excellent health potential. Unfortunately, it is very modestly used in activities aimed at improving the immunity of Polish society. This treatment would be best combined in patients after vaccination and in a certain period before vaccination, which would significantly increase the effectiveness of prophylactic vaccinations.
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Blackwood, Catherine B., Emel Sen-Kilic, Dylan T. Boehm, Jesse M. Hall, Melinda E. Varney, Ting Y. Wong, Shelby D. Bradford et al. « Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection ». Vaccines 8, no 4 (3 novembre 2020) : 647. http://dx.doi.org/10.3390/vaccines8040647.
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Whole cell vaccines are frequently the first generation of vaccines tested for pathogens and can inform the design of subsequent acellular or subunit vaccines. For respiratory pathogens, administration of vaccines at the mucosal surface can facilitate the generation of a localized mucosal immune response. Here, we examined the innate and vaccine-induced immune responses to infection by two respiratory pathogens: Bordetella pertussis and Pseudomonas aeruginosa. In a model of intranasal administration of whole cell vaccines (WCVs) with the adjuvant curdlan, we examined local and systemic immune responses following infection. These studies showed that intranasal vaccination with a WCV led to a reduction of the bacterial burden in the airways of animals infected with the respective pathogen. However, there were unique changes in the cytokines produced, cells recruited, and inflammation at the site of infection. Both mucosal vaccinations induced antibodies that bind the target pathogen, but linear regression and principal component analysis revealed that protection from these pathogens is not solely related to antibody titer. Protection from P. aeruginosa correlated to a reduction in lung weight, blood lymphocytes and neutrophils, and the cytokines IL-6, TNF-α, KC/GRO, and IL-10, and promotion of serum IgG antibodies and the cytokine IFN-γ in the lung. Protection from B. pertussis infection correlated strongly with increased anti-B-pertussis serum IgG antibodies. These findings reveal valuable correlates of protection for mucosal vaccination that can be used for further development of both B. pertussis and P. aeruginosa vaccines.
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Hammer, Adam, Jonathan Eby, Emily Gilbert, Safia Kahn, Daniel Dilling et I. Le Poole. « Vaccination with GD3 synthase provides tumor protection against melanoma in mice (P4461) ». Journal of Immunology 190, no 1_Supplement (1 mai 2013) : 126.14. http://dx.doi.org/10.4049/jimmunol.190.supp.126.14.
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Abstract Expression of GD3 synthase (GD3s) in cells defines upregulated GD3 expression by melanoma tumor cells. GD3 presented in the context of CD1d is recognized by invariant NKT cells, which can generate cytokines conducive to anti-tumor responses. We hypothesized that DNA vaccination with GD3s could induce effective anti-tumor responses targeting GD3. C57BL/6 mice were subjected to weekly gene gun vaccination introducing DNA encoding either GD3s and adjuvant HSP70i, or TRP-1 ee/ng and HSP70i, versus empty vector DNA as control groups. Mice were challenged with 2.5x105 B16 mouse melanoma cells. Tumor growth was followed and any remaining tumor was resected for fluorocytometric analysis of immune infiltrates and cytokine expression by qRT-PCR. hGD3s-based vaccination provided similar protection from a B16 tumor challenge as the positive control group (60 and 62% reduced tumor sizes at 19 days, respectively). hGD3s vaccinated mice showed increased NKT abundance (2.27% ) compared to TRP-1 (1.11%) or empty vector (0.74%) among vaccinated mice. Increased CD8+ (3.3-fold), and CD4+ (1.2-fold) compared to the negative control group were also observed, combined with an increased abundance in IL-4 and IL-17 transcripts. In conclusion, GD3s based vaccination provided anti-tumor protection associated with inflammatory cytokine expression and increased (NK)T cell recruitment to tumor sites, offering an attractive concept for melanoma treatment.
Thèses sur le sujet "Anti-cytokines vaccination"
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Belmellat-Bouadi, Nadia. « Etude de l’efficacité des stratégies d’immunothérapies actives anti-cytokine et évaluation des conséquences de la vaccination anti-TNF dans des modèles infectieux ». Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCD028/document.
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La polyarthrite rhumatoïde (PR) est le rhumatisme inflammatoire le plus fréquent. Cette maladie s’accompagne d’une hyperplasie de la membrane synoviale qui entoure les articulations. La formation du pannus synovial est sous la dépendance de cytokines pro-inflammatoires et pro-angiogéniques. Les immunothérapies anti-TNF utilisées dans le traitement de la PR présentent des inconvénients (perte d’efficacité, risque infectieux), ce qui laisse la place pour le développement d’une stratégie vaccinale anti-TNF. Dans la première partie de mes travaux, nous avons développé des vaccins anti-VEGF afin d’étudier les liens entre angiogenèse et inflammation dans l’arthrite expérimentale au collagène (AEC). Dans la deuxième partie, nous avons développé un vaccin anti-TNF de souris afin d’évaluer les conséquences de la neutralisation du TNF-α par la vaccination dans des modèles infectieux. Le ciblage du VEGF avec un vaccin constitué de VEGF entier ou de peptides du VEGF couplés à la KLH, a permis une protection clinique et histologique dans l’AEC. Dans notre deuxième axe de recherche, nous avons développé un vaccin anti-TNF de souris (TNF-KLH). Ce vaccin est aussi efficace que l’etanercept dans l’AEC, mais n’augmente pas le risque infectieux dans un modèle d’infection à Mycobacterium tuberculosis. Dans le modèle d’infection à Listeria monocytogenes, TNF-KLH n’augmente pas la charge bactérienne et n’induit pas de mortalité, contrairement à l’etanercept. Mes travaux de thèse montrent que la stratégie vaccinale anti-cytokine est efficace dans l’arthrite, et que le ciblage du TNF par une telle stratégie ne semble pas altérer la réponse anti-infectieuse dans nos modèlesRheumatoid arthritis (RA) is the most frequent inflammatory rheumatism. This disease is accompanied by hyperplasia of the synovial membrane surrounding the joint. Pannus formation is controlled by pro-inflammatory and pro-angiogenic cytokines. Anti-TNF immunotherapies used in the treatment of RA presents many drawbacks (loss of efficacy, infections), which leaves some place for the development of an anti-TNF immunization strategy. In the first part of my work, we developed an anti-VEGF vaccine to study the links between angiogenesis and inflammation in collagen-induced arthritis (CIA) model. In the second part, we developed a mouse anti-TNF vaccine to assess the consequences of the neutralization of TNF-α by vaccination in infectious models. Inhibition of VEGF with a vaccine consisting of whole VEGF or VEGF peptide coupled to KLH, showed a clinical and histological protection in the CIA model. In the second part of my work, we developed a mouse anti-TNF vaccine (TNF-KLH). This vaccine is as effective as etanercept in CIA, but does not increase the risk of infection in Mycobacterium tuberculosis model. In Listeria monocytogenes model, unlike etanercept, immunization with TNF-KLH does not increase the bacterial burden and mortality. My work contributed to the development of active anti-VEGF vaccine and our results show a partial protection with this strategy. Also, we demonstrate that targeting TNF by active immunotherapy does not alter the immune response in our models of infections
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Delavallée, Laure. « Vaccination anti-TNF dans la polyarthrite rhumatoïde ». Paris 13, 2009. http://www.theses.fr/2009PA132031.
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La Polyarthrite Rhumatoïde (PR) est le rhumatisme inflammatoire le plus fréquent, conséquence d’une inflammation chronique articulaire accompagnée d’une destruction tissulaire. Bien que son étiologie précise ne soit pas connue, il est admis un rôle majeur du déséquilibre de la balance cytokinique dans sa pathogenèse. Ainsi, l’amélioration des connaissances des mécanismes physiopathologiques de la PR a permis le développement d’immunothérapies ciblant les cytokines pro-inflammatoires, et notamment le TNF-α (anticorps monoclonaux, récepteur soluble). Ces traitements ciblés anti-TNF ont démontré leur grande efficacité dans la PR. Cependant, l’absence de réponse ou l’échappement secondaire de certains patients à ces traitements laisse l’opportunité de développer des stratégies alternative pour bloquer cette cytokine. L’objectif principal de nos travaux de recherche a consisté à démontrer le concept de la vaccination anti-TNF (TNF-K) dans le traitement d’une polyarthrite expérimentale, d’évaluer son degré d’efficacité ainsi que de déterminer expérimentalement le ratio bénéfice/risque d’une telle stratégie. Nous avons montré l’efficacité clinique d’un traitement par TNF-K dans un modèle de polyarthrite expérimentale. Nous montrons que les taux d’anticorps anti-TNF ont une évolution « en cloche » dans le temps. Nous montrons que le blocage du TNF-α est suffisant pour observer les effets escomptés mais laissent une production résiduelle de cytokine active. Nous apportons des arguments en faveur d’une réponse T anti-TNF-K dirigée contre la KLH et non le TNF-α, et de l’incapacité du TNF-α seul à générer la réascension tardive des anticorps chez les souris vaccinées. L’ensemble de ces résultats décrit un profil immunologique favorable au TNF-K en terme de rapport bénéfice/risque. En outre, nous rapportons l’évolution des arthrites sur un an de souris transgéniques pour le hTNF-α jamais signalée dans la littératureRheumatoid Arthritis (RA) is the most frequent inflammatory rheumatism, consequence of chronic articular inflammation followed by articular destruction. Although its precise etiology is still unknown, major role of cytokines imbalance was demonstrated in its pathogenesis. Better comprehension of RA pathophysiological mecanisms induced development of immunotherapies targeting pro-inflammatory cytokines, in particular TNF-α (monoclonal antibodies, soluble receptor). These targeted treatment to TNF have demonstrated their efficacy in RA. However, primary unresponsiveness or secondary escape to these treatments can occur and give rise to new alternative strategies to target this cytokine. The main objective of our research work consisted in demonstrating anti-TNF vaccination (TNF-K) concept in treatment of experimental polyarthritis, in evaluating its degree of efficacy as well as experimental benefit/risk ratio of such a strategy. We show clinical efficiency of TNF-K treatment in polyarthritis experimental model. We show a bell-shaped evolution of neutralizing anti-TNF antibodies during time. We demonstrate that TNF blockade is sufficient to observe the expected effects, but still leave residual production of active cytokine. We bring evidence of an anti-TNF-K cellular response to KLH, but not to TNF, and we showed that only TNF injection do not induce the production of new neutralizing anti-TNF antibody in immunized mice. All these data are consistent with a favorable immunological profile of TNF-K regarding benefit/risk ratio. Besides, we report for the first time evolution of human TNF transgenic mice arthritides on one year follow-up
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Conde, García Eva. « Anti -IL-4, -IL-13 and -IgE vaccination for the treatment of allergic diseases ». Thesis, Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2020SORUS011.pdf.
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Les allergies représentent un problème de santé majeur avec une prévalence en nette augmentation et pour lesquelles il n’existe pas de thérapie à longue durée. L’IL-4, l’IL-13 et l'IgE jouent un rôle clé dans les réactions allergiques. Ces cibles thérapeutiques ont été validées en clinique, grâce aux anticorps monoclonaux. Néanmoins, leur utilisation reste contraignante de par leur coût excessif et la nécessité de réinjections fréquentes. L’objectif de cette thèse a été de développer des vaccins contre l’IL-4, l’IL-13 et l’IgE, appelés kinoïdes, et d’apporter la preuve de concept de l’efficacité dans des modèles d’asthme et de choc allergique. Nous avons démontré qu’une vaccination combinée contre l’IL-4 et l’IL-13 permet de réduire les taux d’IgE, l’hyperréactivité bronchique, l’éosinophilie et la production de mucus dans un modèle murin d’asthme chronique. De plus, nous avons montré qu’une vaccination avec des kinoïdes IL-4/IL-13 humains induit des anticorps neutralisants anti-IL-4 et IL-13 humaines et et réduit les niveaux d’IgE dans des souris humanisées pour l’IL-4, l’IL-13 et IL-4Ra. Nous avons également développé un vaccin conjugué contre l’IgE humaine. Nous avons montré que ce vaccin induit une forte production d’anticorps neutralisant anti-IgE humains, dans une nouvelle souche de souris humanisée pour l’IgE et le récepteur FceRI. Une vaccination des souris humanisées IgE/FceRI avec le kinoïde IgE humain réduit fortement les taux d’IgE et protège contre un choc anaphylactique induit par les IgE. L’ensemble de ces études démontre qu’une vaccination contre l’IL-4, l’IL-13 ou l’IgE pourrait représenter une solution thérapeutique contre les maladies allergiquesAllergies represent major public health problems of increasing prevalence and for which there is still no efficient long-term therapy. IL-4 and IL-13, and IgE play key roles in allergic reactions, and therefore represent good therapeutic targets. These targets have been clinically validated with approved monoclonal antibodies (mAb). However, use of mAb is limited by high cost and the need to perform repeated injections. Therefore, there is a clear need to improve current strategies in order to reach long term effects. The objective of this thesis was to develop anti-IL-4, anti-IL-13 and anti-IgE vaccines called kinoids, and provide a proof-of-concept of their safety and efficacy. We developed conjugate vaccines against IL-4 and IL-13, and demonstrated their prophylactic and therapeutic efficacy in reducing IgE levels, airway hyperresponsiveness, eosinophilia and mucus production in a house dust mite-induced mouse model of asthma without any detectable adverse effect. The human version of the IL-4/IL-13 kinoid was also efficient at neutralizing human IL-4 and IL-13, and reducing IgE levels in mice humanized for IL-4, IL-13 and their common receptor subunit IL-4Ra. In addition, we also developed a conjugate vaccine against human IgE. We showed that this anti-IgE vaccine induces long-term production of anti-human IgE neutralizing antibodies in a novel mouse strain we characterized and which is humanized for IgE and its high-affinity receptor FceRI. Anti-human IgE vaccination reduced hIgE, and fully protected against IgE-mediated anaphylaxis. Altogether, our results showed that vaccination against IL-4, IL-13 and IgE could be a valuable strategy to target allergic disorders