Дисертації з теми "Mucolas vaccination"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-45 дисертацій для дослідження на тему "Mucolas vaccination".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Heritage, Philippa Louise. "Mucosal vaccination with a novel microparticle delivery system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0003/NQ42849.pdf.
Повний текст джерелаVento, Kevin Leon. "Assessment of protective immunity following mucosal vaccination with Pseudomonas aeruginosa." Thesis, St George's, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408031.
Повний текст джерелаMoors, Adam. "Antibody mediated mucosal defences in the female genital tract." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368058.
Повний текст джерелаRahman, Muhammad Jubayer. "Mucosal immunity against mycobacterial infection." Doctoral thesis, Stockholms universitet, Wenner-Grens institut, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-39170.
Повний текст джерелаAt the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript
Easeman, Richard. "Induction of mucosal immune responses in the horse." Thesis, Open University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389312.
Повний текст джерелаHall, L. J. "Phenotypic and functional characterisation of innate and adaptive immune responses after mucosal vaccination." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599868.
Повний текст джерелаFalkeborn, Tina. "Nasal vaccination using novel mucosal adjuvants : with main focus on influenza A virus." Doctoral thesis, Linköpings universitet, Avdelningen för mikrobiologi och molekylär medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-117981.
Повний текст джерелаVazquez, Thomas. "Evaluation préclinique d'un protocole vaccinal anti-VIH utilisant des pseudo-particules rétrovirales recombinantes administrées par voies muqueuses et étude des mécanismes immunologiques associés." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066321.
Повний текст джерелаCurrently no HIV vaccine elicit full and stable protection against viral acquisition. In view of the failures until now, new vaccines strategies were developed. Among these, VLP have the advantage to be highly immunogenic because of their particulate structure mimicking native pathogens and safe because of the lack of viral genome.This thesis work aims to develop and evaluate a VLP-based vaccine strategy by mucosal administration in order to initiate systemic and local humoral and cellular responses. In this study, we showed that the mucosal administration is mandatory to generate a strong local immunity. Moreover, our results show that particular form of the antigen is crucial in the generation of the quality of the immune response, generating strong TFH response, polyfunctional T-cell responses in the mucosa and a strong and stable humoral response characterized by high-quality antibodies.We also investigated mechanisms involved in the generation of immune responses following IN VLP injections. We determined which cells take in charge VLP and their role in the followed immune responses. Our preliminary results show many innate immune cells in the lungs, such as alveolar macrophages and neutrophils, have an important role in the particles uptake, limiting TFH response and potentially the followed humoral response.Finally, this thesis work will show the determining role of the mucosal route of immunization and the particulate form antigen for the development of an HIV vaccine
Biswal, Jitendra Kumar. "Evaluation of mucosal immunity in FMDV vaccinated and infected cattle." Thesis, Royal Veterinary College (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572448.
Повний текст джерелаMcGuire, Carolann. "Mucosal vaccination using a crude antigen and a synthetic peptide in the Trichinella spiralis model." Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285567.
Повний текст джерелаRydell, Niclas. "Development of a New Oral Vaccine against Diphtheria and the Study of its Immunogenicity in Mouse and Man." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4629.
Повний текст джерелаBarri, Adriana. "Effects of Cytosine-phosphate-Guanosine Oligodeoxynucleotides (CpG-ODN) on vaccination and immunization of neonatal chickens." Texas A&M University, 2004. http://hdl.handle.net/1969.1/1550.
Повний текст джерелаStrindelius, Lena. "Mucosal Vaccination Using Polyacryl Starch Microparticles as Adjuvant with Salmonella enteritidis as a Model Pathogen." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3493.
Повний текст джерелаHeidland, Judith [Verfasser]. "Chitosan Nanoparticles for Mucosal Vaccination – Understanding the Particle Formation Process and Formulation for Nasal Application / Judith Heidland." Kiel : Universitätsbibliothek Kiel, 2018. http://d-nb.info/116401255X/34.
Повний текст джерелаTruter, Erika Mare. "Chitosan derived formulations and EmzaloidTM technology for mucosal vaccination against diphtheria : nasal efficacy in mice / Erika M. Truter." Thesis, North-West University, 2005. http://hdl.handle.net/10394/858.
Повний текст джерелаThesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
Logerot, Sandrine. "Utilisation de l’interleukine-7 en immunothérapie chez des patients VIH-mauvais répondeurs immunologiques et comme adjuvant de vaccination muqueuse chez le macaque rhésus." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB111.
Повний текст джерелаHighly Active Antiretroviral Therapy (HAART) has led to significant reduction of HIV-associated mortality by maintaining an undetectable viral load and inducing progressive CD4-T cell restoration. However, some patients, defined as poor immunological responders (PIR), fail to restore their CD4 counts to 500cells/µL during treatment, a threshold considered as the protective against AIDS related or non AIDS related malignancies, opportunistic infections and cardiovascular events. Interleukin-7 (IL-7), an essential cytokine for thymopoïesis and T cell homeostasis has been used in clinical trials aimed at restoring and maintaining CD4 counts in PIR patients. The first part of my thesis project aimed at assessing the impact of IL-7 therapy on circulating HIV reservoir. In the clinical study we worked on (INSPIRE 3, Cytheris), cycles of IL-7 injections led to a significant increase of the number of circulating CD4 and CD8 T-cells, with a predominance of naïve and central memory T cell expansion. We have shown that one cycle of IL-7 injections induced a significant increase in the number of circulating infected cells 28 days and 3 months post-injections. However, despite a significant increase in the frequency of infected CD4 T-cells 28 days post-injections, we observed a significant decrease of HIV-DNA load in CD4 T-cells in the majority of patients 3 months after the therapy initiation. These data suggest a partial elimination of HIV infected cells. After the second cycle of IL-7 injections, we did not observed any change in the number or frequency of circulating infected cells, suggesting a differential impact of the two IL-7 injection cycles on the dynamics of circulating HIV-reservoir. Finally, considering that some patients developed anti-IL-7 neutralizing antibodies (Nab) after the second cycle of IL-7 injections, we looked for predictive factors of this immunogenicity and analyzed its physiological consequences in vivo. The only parameter that distinguished Nab and non-Nab patients was the extent of CD4 T-cell reconstitution during the first cycle of therapy. This suggests that a better response to IL-7 also facilitates the development of auto-antibodies to the cytokine. However, these antibodies were only transiently detectable after the second cycle of therapy. Moreover, the appearance of Nab was associated with a significant but transient decrease of thymocyte proliferation, suggesting a functional impact of these antibodies on the endogenous IL-7 function. Systemic injection of IL-7 induces circulating T cells homing from the blood into lymphoid and non-lymphoid tissues. In the second part of my thesis project, I evaluated whether this cytokine could be used as an adjuvant when sprayed on the vaginal mucosa. Ten micrograms of IL-7 directly sprayed in the vaginal tract of rhesus monkeys induced, 48h after administration, the production of a large pattern of chemokines in the vaginal chorion and epithelium. This chemokine expression was accompanied by massive homing of CD4 and CD8-T cells, macrophages, dendritic cells and NK cells in the vaginal mucosa, suggesting an increased immunological vigilance. Finally, the adjuvant potential of this cytokine was confirmed by analyzing local humoral immune response after vaginal administration of antigens 48h following IL-7 spray. In cervicovaginal washes (CVL) of treated animals, we observed a faster, stronger and longer-lasting specific IgA and IgG response than in control animals, highlighting the capacity of IL-7 to prepare the vaginal mucosa response to local antigen stimulation
Pereau, Buffin Sophie. "Évaluation des pseudo-particules grippales dans un but de vaccination par voies muqueuses." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1087.
Повний текст джерелаThe influenza virus infects the mucous membranes of the respiratory tract. An intranasal vaccine induces an immune response close to the one induced by the natural infection by blocking the virus directly at the site of infection and allows needle-free vaccination. In addition, vaccines based on Virus-like Particles (VLP) produced in cells represent an interesting alternative to the traditional egg-based vaccine. VLPs are non-replicative particles that mimic the virus. Studies on influenza VLPs have shown protection by the intranasal route without adding an adjuvant. During my thesis, a platform for the production of influenza VLPs composed of the hemagglutinin, the neuraminidase and the M1 matrix proteins was developed by transient transfection of mammalian cells. Immunizations of BALB/c mice showed that the purified and characterized type A and B VLPs were immunogenic at low doses by the intramuscular route. The intranasal administration of VLPs with the B subunit of cholera toxin as a mucosal adjuvant resulted in serum antibody levels comparable to those obtained by intramuscular immunization but also a strong IgA response in the mucosal secretions. In addition, VLP yield was found to be strain-dependent and linked to the HA and NA proteins on the surface of the particle. To overcome this problem, a quadrivalent vaccine based on two bivalent VLPs each expressing two different HAs and NAs at the surface was produced, demonstrating the flexibility of this platform
Delph, Katherine. "Comparison of immunologic responses following intranasal and oral administration of a USDA-approved, live-attenuated Streptococcus equi vaccine." Thesis, Kansas State University, 2016. http://hdl.handle.net/2097/32595.
Повний текст джерелаDepartment of Clinical Science
Elizabeth Davis
Background: While there is a commercially-available vaccine for Streptococcus equi subsp. equi licensed for the intranasal route of administration, some equine practitioners are administering this vaccine orally despite a lack of evidence for its efficacy by this route of administration. Objectives: To compare systemic and local immune responses following intranasal or oral administration of the USDA-approved, live-attenuated Streptococcus equi subspecies equi vaccine (Pinnacle IN®, Zoetis, Florham Park, New Jersey). Study Design: Experimental, randomized clinical trial Methods: Eight healthy horses with low Streptococcus equi M protein (SeM) titers (<1:1600) were randomly assigned to an intranasal or oral two-vaccine series. SeM-specific serum immunoglobulins G (IgG) and A (IgA) and nasal secretion IgA were assessed using a commercially-available ELISA (Equine Diagnostic Solutions, LLC, Lexington, Kentucky) and a novel magnetic microsphere assay utilizing fluorescence. A general linear mixed models approach was used for statistical data analysis. Results: As expected, intranasal vaccinates showed substantial increases in both serum SeM-specific IgG and IgA levels post-vaccination (P=0.0006 and P=0.007, respectively). Oral vaccinates showed an increase in serum SeM-specific IgG post-vaccination (P=0.0150), though only one-third the magnitude of intranasal vaccinates. Oral vaccinates showed no evidence of change in SeM-specific IgA post-vaccination (P=0.15). Main Limitations: Changes in mucosal antibody responses were not identified in this study which may be related to small change in antibody response, timing of sample collection, or method of nasal secretion collection. Conclusions: Results indicate that intranasal or oral vaccine administration resulted in increased serum SeM-specific IgG, though the magnitude of response differed between routes.
Daley, Alexandra Clare. "A Comparison of Systemic and Mucosal Immune Responses Following Oral Vaccination with Genetically Modified Strainds of Enterotoxicgenic Escherichia Coli." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499201.
Повний текст джерелаVan, der Westhuizen Elaine. "Chitosan derived formulations and EmzaloidTM technology for mucosal vaccination against diphtheria : oral efficacy in mice / Elaine van der Westhuizen." Thesis, North-West University, 2004. http://hdl.handle.net/10394/633.
Повний текст джерелаThesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
Gutjahr, Alice. "Évaluation de combinaisons de ligands de PRR et de particules biodégradables pour la vaccination muqueuse." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1325.
Повний текст джерелаThere are many barriers to the development an effective HIV vaccine. The use of adjuvants is a promising option to overcome these obstacles. In this context, the objective of this PhD is the evaluation of combinations of PRR ligands and biodegradable particles for mucosal vaccination.The first part of this study aimed at assessing the added value of hybrid molecules composed of two PRR ligands compared to the co-administration of the two agonists. TLR7 and TLR2 stimulating molecules followed by TLR7 and NOD2 were evaluated. We demonstrated the interest of the association of PRR ligands within the same molecule for the induction of systemic and mucosal immune responses.Recent studies showed the interest of STING agonists as a vaccine adjuvant. We investigated the induction of immune responses by STING agonists administered parenterally or mucosally. We confirmed the strong potential of STING ligands for the induction of cellular and mucosal responses.In these studies, we demonstrated that the interest of vectorization of PRR agonists depends on the molecule. Indeed, although the encapsulation of a TLR7/TLR2 hybrid molecule has no impact on the induced immune response, the vectorization of STING agonists potentiates their immunostimulatory effect.Finally, we showed that the route of administration has an impact on the immune response induced. In order to better understand the mechanisms involved, a biodistribution study of PLA NP formulations after systemic or mucosal administration was performed
Gayet, Rémi. "Impact de la réponse IgA dans une nouvelle stratégie de vaccination muqueuse contre Salmonella et dans la régulation de la réponse adaptative." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSES015/document.
Повний текст джерелаThe enterobacteria Salmonella species are divided into several serovars such as Typhimurium, Enteritidis, Typhi and Paratyphi which are the major causative agents of either gastroenteritis or typhoid fever. They are responsible for more than 90 million cases and 400 000 deaths each year. The increase in multi-drug resistant strains requires the implementation of prophylactic mucosal vaccines. Besides, the intestinal environment is characterized by a balance between immune tolerance and inflammatory response tightly regulated by secretory immunoglobulins (Ig) A. Mucosal IgA are mainly dimeric, serum IgA monomeric and two IgA isotypes have been described in humans: IgA1 and IgA2. We firstly explored the functions of the different isotypes and isoforms of human IgA. We pointed out a pro-inflammatory role of IgA2 whereas IgA1 rather oriented the immunity towards an anti-inflammatory response. We have also highlighted both the regulation of IgA receptors expression by IgA and an IgA/CD8 cytotoxic T cells axis. We also designed a multivalent vaccine against Salmonella by coupling two antigens – SseB and OmpC – to secretory Ig. We pointed out solid specific humoral and cellular responses against both these antigens coupled to either IgA or IgM after intra-nasal immunization in mucosal but also systemic compartments. We have also demonstrated the possibility to preserve and increase the antigen immunogenicity with a multivalent vaccine. This thesis thus paves the way for new secretory Ig-vectorized mucosal vaccines. In addition, the immune response could be modulated through the chosen isotype or isoform and the differences in immune activation generated by structural changes in IgA could shed some light on their role in mucosal homeostasis
Grieves, Jessica Louise. "Respiratory Syncytial Virus: Rodent Models and Vaccine Development." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1354147313.
Повний текст джерелаXu, Lin. "HIV-1 mucosal immunity : from infection to prevention : HIV-1 envelope gp41 conserved region P1 modulates the mucosal innate immune response and acts as a potential mucosal adjuvant The HIV-1 viral synapse signals human foreskin keratinocytes to secrete thymic stromal lymphopoietin facilitating HIV-1 foreskin entry By shaping the antigen binding site in IgA, the CH1α domain is crucial for HIV-1 protection in highly exposed sero-negative individuals The antigen HIV-1 envelope gp41 conserved region P1 can act as mucosal adjuvant by modulating the innate immune response". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB071.
Повний текст джерелаMucosal vaccination, especially intranasal administrated ones, has been considered to be ideal for protection from pathogens invading through mucosal sites. However, the lack of specific adjuvant and insufficient acknowledgement of nasal immune system limits the development of vaccine. P1, a conserved region of gp41 envelope glycoprotein, was recently developed into a prophylactic HIV-1 vaccine immunized via both the intramuscular and intranasal routes. It showed high efficiency in pre-clinical and phase I clinical trial due to induction of P1 specific mucosal IgA with transcytosis blocking activity and IgG inducing antibody dependent cell cytotoxicity. In this study, we characterized the immunological mechanism underneath P1-vaccine in nasal mucosa. Firstly, we demonstrated that P1 initiate immune responses by inducing nasal epithelial cells to secret the Th2 cytokine Thymic Stromal LymphoPoietin (TSLP). TSLP has been reported to be a strong mucosal adjuvant, and its receptor TSLP-R plays a critical role in IgA response. We showed that P1 induce TSLP expression via the interaction with galactosyl ceramide, the receptor of HIV-1 mucosal entry. Furthermore, we identified Calcineurin/NFAT signaling pathway and microRNA-4485 as important players in the regulation of TSLP production induced by P1. Secondly, we showed that P1 modulates innate immune responses by activate dendritic cells (DCs). P1 stimulation results in enhanced expression of costimulatory molecules on DCs. Furthermore, the secretion of IL-6, IL-10 were increased, while IFN-γ was reduced, indicating that P1 activated DCs polarize into a Th2 and IgA prone phenotype. In addition, IL-8, CCL20, CCL22 were produced indicating a capacity at recruiting immune cells to mucosal surface for initiation of an adaptive immune response. MMP-9 was also produced allowing degradation of the extracellular matrix and facilitating the migration of immune cells out of the mucosa. Stricingly, a TSLP autocrine loop was observed as P1 induced DCs to secret TSLP and meanwhile, enhanced DC expression of TSLP-R. Finally, P1 activated DCs enhanced the proliferation of CD4+ T cells. In conclusion, we demonstrated that P1 is a multi-functional protein with a great interest for vaccine development, not only as an antigen for vaccine candidate, but also as a potential adjuvant that can be combined to other mucosal vaccines
Rowe, John Christopher. "Targeting Neutrophils to Improve Protection by Sublingual Vaccines." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1612190976457585.
Повний текст джерелаWhite, Andrew David. "Immune responses induced by Mycobacterium bovis BCG, and modified vaccinia virus Ankara expressing mycobacterial antigen 85A, when delivered as mucosal or systemic vaccinations to non-human primates." Thesis, Open University, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.700136.
Повний текст джерелаPrice, Gregory A. "Immunogenicity of the Gonococcal Transferrin Binding Proteins." VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd_retro/76.
Повний текст джерелаRochereau, Nicolas. "Evaluation de stratégies vaccinales anti-VIH-1 basées sur l’utilisation de SIgA comme molécules d’adressage muqueux." Thesis, Saint-Etienne, 2012. http://www.theses.fr/2012STET005T.
Повний текст джерелаSecretory IgA (SIgA) are the main effectors of the mucosal immune response. More, SIgA have the capacity to adhere to the apical membrane of M cells present in the intestinal and nasal mucosa. After binding to M cells, SIgA are transported from the intestinal lumen to the GALT by a reverse transcytosis mechanism. In this work, I have assessed the capacity of SIgA to effectively deliver a vaccine antigen through the epithelial barrier via M cells to sub-mucosal dendritic cells (DCs). Precise mechanisms and the IgA-specific receptor(s) for reverse transcytosis have not yet been identified. In this work, I identified the receptors involved in SIgA reverse transcytosis. Both dectin-1 and siglec-5 allow the transport of the Cα1 domain of SIgA by murine an human M cells in vitro and also in vivo. This work is currently undergoing to immunity (publication 1) and should also be patented. Next, I tried to use the reverse transcytosis mechanism mediated by M cells to efficiently deliver an HIV-1 antigen by mucosal routes. We applied results obtained using SIgA as a vaccine vector for M cells targeting. This approach should help to protect antigen in the mucosal environment. Applications of this approach to oral and nasal immunisation are described in the incomplete publication 4. During any PhD, I was able to demonstrate that SIgA reverse transcytosis is a physiological mechanism depending on sugar receptors. I was also able to demonstrate that their use could be a very promising vaccine approach especially for mucosa] diseases or pathogens as HIV
Fasquelle, François. "Etude de la délivrance d’antigènes dans les voies aériennes en utilisant des nanoparticules de maltodextrine lipidées." Thesis, Lille, 2020. https://pepite-depot.univ-lille.fr/LIBRE/EDBSL/2020/2020LILUS024.pdf.
Повний текст джерелаThe mucosal routes of immunization present several advantages compared to classical injection routes. Indeed, besides a better compliance towards patients, these routes possess their own immune system, also known as the Mucosal Associated Lymphoid Tissue (MALT), able to trigger a local mucosal response after immunization. This tissue is mainly located in the nasal and intestinal mucosa, where it is spread in small extents called Follicular Associated Epithelium (FAE). On their apical surface, the FAE contain specialized epithelial microfold cells (or M cells), whose role is to survey potential infections by sampling pathogenic fragments, and which overlay a lymphocyte and antigen presenting cells (APC) zone. Then, when an infection occurs, M cells sample and translocate antigenic fragments to CPA, which could therefore trigger lymphocyte maturation and the initiation of the subsequent immune response. This activation will lead to both humoral and cellular immunity in the infected epithelium and could also spread to distant mucosa. As many pathogens infect the body through mucosa, this way of immunization is often considered.Adjuvants are frequently added to subunit vaccines to enhance their immunogenicity toward APC. Indeed, despite their lower toxicity, they are also less immunogenic than live-attenuated vaccines. However, the administration of classical adjuvanting molecules, such as toxins or immunostimulating emulsions, via mucosal routes, has often led to serious adverse effects. Therefore, the alternative use of delivery systems to deliver antigen in APC after mucosal administration is more and more studied.Antigen delivery systems include immunomodulating particles, and inert delivery systems. The first ones can enhance the mucosal antigen bioavailability by vectorizing antigens to APC, and at the same time trigger intracellular pro-inflammatory pathways, to drive the Th1/Th2 immune balance. Among them, virus-like particles (VLP), saponin-based emulsions (ISCOMs) or MPL-containing liposomes are the most represented in clinical trials. However, their mucosal administration can lead to the same adverse effects than classical immunostimulating molecules. In parallel, true delivery systems can enhance the antigens immunogenicity by increasing their intracellular delivery, thus mimicking a natural infection. They are therefore far less toxic for the mucosa than immunomodulating particles but need to be more efficient in the mucus penetration, in the antigen association and in the APC intracellular delivery.During this thesis, we deciphered the mechanisms allowing cationic and lipidated maltodextrine nanoparticles (NPL) to deliver antigens after nasal administration.We first evaluated the ability of NPL to cross the airway mucus barrier, compared to mucopenetrant particles (PEG-coated PLGA or PLGA-PEG) and mucoadherent particles (chitosan-coated PLGA or PLGA-CS), by measuring their displacement in reconstituted mucus. We observed that in presence of the phospholipid core, the NPL were able to move in the mucus, while PLGA-CS NPs remained stuck in the gel. Moreover, we observed that the NPL uptake and the protein delivery in airway epithelial cells were not impaired by the presence of mucins, contrary to PLGA-CS that were hindered by the mucins, and to PLGA-PEG which were not taken up by the cells, due to their neutral surface charge. We finally demonstrated that the NPL mucopenetration was allowed thanks to steric and repulsive electrostatic forces between the anionic phospholipid core and the mucins.In parallel, we studied the mechanisms allowing the NPL to enhance the immunogenicity of subunit antigens after nasal administration, with a highlight on the importance of the NP’s density [...]
Dhakal, Santosh. "Development and Evaluation of Nanoparticle-based Intranasal Inactivated Influenza Virus Vaccine Candidates in Pigs." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1529829066502348.
Повний текст джерелаThiam, Fatou. "Effets de différents adjuvants de la famille de la toxine du choléra sur les lymphocytes T CD4 dans un modèle murin d'immunisation intrarectale avec des pseudoparticules virales de rotavirus." Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00867205.
Повний текст джерелаMei, Henrik Eckhard. "Analysen zur differentiellen Plasmazellhomöostase beim Menschen." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2010. http://dx.doi.org/10.18452/16048.
Повний текст джерелаHumoral memory, i.e. persistence of specific antibody titers, is provided by plasma cells in the bone marrow, which are generated from activated B cells during immune responses. At this, immediate plasma cell precursors, the plasmablasts, migrate via the blood to the bone marrow. Using cytometric detection of antigen-specific plasmablasts, synchronous circulation of waves of recently generated, migratory plasmablasts and non migratory plasma cells with a mature phenotype was demonstrated one week after tetanus vaccination. Circulating plasmablast and plasma cell numbers were always in homeostasis, so that the stoichiometric mobilization of old bone marrow plasma cells by recently generated plasmablasts was hypothesized. This plasma cell replacement mechanism is herein described for the first time as an adaption mechanism of the humoral memory that allows incorporation of new antibody specificities while maintaining pre-existing ones. In immunological steady state, very low numbers of plasmablasts are detectable in any donor. These express IgA and receptors for mucosal homing, alpha4beta7 integrin and CCR10, and therefore most likely migrate into mucosal plasma cell depots and do not interfere with plasma cells of the bone marrow, preserving the stability of humoral memory during steady state. Hence, adaption of humoral memory is only possible during systemic immune reactions. Circulating mucosal plasmablasts produced during steady state remain detectable in patients with rheumatoid arthritis during B cell depletion therapy as well as in asplenic patients. Hence, this type of plasmablasts is self-sufficiently generated from mucosal B cells that are refractory to B cell depletion therapy. This work demonstrates a hitherto disregarded complexity of peripheral plasmablast and plasma cell subsets in healthy humans, with implications for the regulation of induction and maintenance of humoral memory.
David, Shannon Christa. "Enhancement of pathogen-specific immunity following co-administration of whole inactivated respiratory vaccines." Thesis, 2018. http://hdl.handle.net/2440/117960.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 2018
Zhu, Xiaoping. "Mucosal vaccination against herpesviral infection." 1997. http://catalog.hathitrust.org/api/volumes/oclc/39729337.html.
Повний текст джерелаAlves, Pedro Luís Cardoso. "Refinement of a mucosal vaccination strategy against neosporosis." Master's thesis, 2017. https://hdl.handle.net/10216/107645.
Повний текст джерелаAlves, Pedro Luís Cardoso. "Refinement of a mucosal vaccination strategy against neosporosis." Dissertação, 2017. https://hdl.handle.net/10216/107645.
Повний текст джерелаTakada, Ayato. "Experimental Study on Mucosal Vaccination of Animals against Viral Infections." Doctoral thesis, 1996. http://hdl.handle.net/2115/32735.
Повний текст джерелаRibeiro, Olga Maria Fernandes Borges. "Alginate coated chitosan nanoparticles as adjuvant for mucosal vaccination with hepatitis B antigen." Doctoral thesis, 2007. http://hdl.handle.net/10316/315.
Повний текст джерелаA nova geração de vacinas são, na maioria dos casos, resultado dos rápidos avanços que se têm verificado nos últimos anos na área da biologia molecular e da imunologia, permitindo o uso da biotecnologia na produção de proteínas recombinantes com acção imunológica protectora. A vacina contra o vírus da hepatite B é disso o melhor exemplo. Esta vacina foi licenciada pela primeira vez em 1981, sendo nesta altura um produto derivado do plasma de portadores crónicos da hepatite B. Só mais tarde, em 1986, o mesmo antigénio, uma proteína de superfície do vírus da hepatite B, começou a ser produzido em sistemas de cultura celular. A vacina da hepatite B foi a primeira vacina recombinante a ser licenciada e a sua concepção tem servido de modelo ao desenvolvimento de novas vacinas, nomeadamente em doenças provocadas por vírus. Por outro lado, tem sido constatado pela comunidade científica que estas vacinas recombinantes são em geral antigénios fracos e por isso necessitam de ser administrados conjuntamente com substâncias que ampliem o seu efeito, os adjuvantes. Assim, paralelamente ao crescente desenvolvimento, que se tem verificado nos últimos anos, da tecnologia para o desenvolvimento e produção de novas vacinas, assiste-se também a uma crescente investigação na descoberta de adjuvantes mais seguros e potentes que tornem essas vacinas mais eficazes e estáveis. O termo “adjuvante” vem do termo latim adjuvare que significa ajuda. Recentemente, num livro editado por Virgil Schijns e Derek O’Hagan, dois de entre os maiores especialistas na área das vacinas e adjuvantes, o termo adjuvante é definido tendo em conta o seu efeito biológico. Estes investigadores classificam-nos em duas categorias principais: os adjuvantes cuja função principal é o controlo da biodisponibilidade da vacina nos tecidos linfoides (“delivery mechanism”) e os imunopotenciadores que têm uma acção directa sobre componentes da resposta imune inata. O presente trabalho teve por objectivo desenvolver um sistema nanoparticular (“delivery mechanism”), com potencial para a encapsulação de vacinas resultantes da tecnologia recombinante, com a finalidade de transportar e controlar a apresentação do antigénio nos tecidos linfóides. Tem sido referido por alguns investigadores que o sistema de libertação de vacinas ideal deve ter em conta o fenómeno de maturação da afinidade, que ocorre durante uma resposta imune. Quando a concentração de um antigénio é reduzida, as células com elevada afinidade para os receptores são estimuladas selectivamente. De acordo com este modelo, o padrão do sistema ideal deve imitar os perfis de concentração de antigénios que são observados no decurso de uma infecção natural: elevadas doses de antigénios, nos primeiros dias da administração, seguidos por um período em que há decréscimo da quantidade de antigénios. A biodisponibilidade inicial dos antigénios irá influenciar a extensão da formação da memória das células T, enquanto a subsequente diminuição dos antigénios irá beneficiar o desenvolvimento da maturação da afinidade dos anticorpos. Por outro lado, será útil fazer uma reflexão sobre qual a via de administração mais indicada para a administração de vacinas. Visto que as mucosas, nomeadamente a oral, a nasal, a pulmonar e genitourinária, são os locais por onde entram a maior parte dos microorganismos patogénicos, então a protecção contra esses microorganismos será mais eficiente pela presença de anticorpos nas secreções locais do que no soro. Alguns autores referem mesmo que a imunoglobulina A secretória (sIgA) local previne de forma mais eficiente, não só a colonização dos tecidos das mucosas, mas também a entrada de microorganismos na corrente sanguínea, quando comparada com a acção dos anticorpos sistémicos. Por outro lado, a indução de anticorpos nas mucosas não parece ser possível através da administração subcutânea ou intramuscular, usadas vulgarmente nos esquemas de vacinação. As evidências científicas, até hoje reunidas, indicam que, para haver indução de anticorpos (sIgA) nas mucosas, a administração do antigénio deve ser feita através das mucosas que se encontram revestidas por tecido linfoíde. Por esta razão, parece desejável que a próxima geração de vacinas, particularmente para os microorganismos patogénicos que invadem o organismo através das superfícies das mucosas, deve ser desenvolvida ou optimizada tendo em atenção a potencial indução de uma resposta imune nas mucosas. Para além da importante vantagem apresentada anteriormente, a administração através das mucosas, particularmente a administração oral, tem sido apontada como a via mais natural para introdução de fármacos no organismo, a de mais fácil acesso e sem os inconvenientes de outras vias de administração, como sejam os riscos de infecção por utilização de agulhas contaminadas, riscos de efeitos hemolíticos ou possível dor durante a administração. Para além disso, a via oral é sem dúvida a melhor aceite, nomeadamente pelas crianças que são a população alvo da maioria das vacinas. Acresce ainda referir que a vacinação em larga escala, num curto espaço de tempo, seria muito facilitada se tivéssemos vacinas orais em que, para a sua administração, não fossem necessários técnicos especializados. É o caso de situações de bioterrorismo, de ameaças de surtos infecciosos ou, simplesmente, o caso de países não industrializados que, por escassez de recursos humanos e também financeiros, continuam a ter taxas elevadas de prevalência de doenças para as quais já existem vacinas eficazes, como por exemplo de hepatite B. A administração oral de macromoléculas como o DNA, as proteínas e os peptídeos tem-se mostrado ineficaz, conduzindo a que, em alternativa, esta classe de fármacos seja administrado por uma das vias parentéricas. A limitada biodisponibilidade oral deve-se fundamentalmente a três ordens de razões. Por um lado ao extensivo metabolismo pré-sistémico a que estão sujeitos, devido à degradação enzimática que sofrem antes e durante os processos de absorção, não só ao nível do lúmen, como da mucosa gastrointestinal. A segunda barreira encontrada, prende-se com as fracas características de absorção destes fármacos e, por último, a terceira razão terá a ver com o efeito da primeira passagem pelo fígado (hepatic first pass effect). Consciente destas dificuldades, a comunidade Científica tem procurado novos sistemas terapêuticos, que permitam contornar ou minimizar as condições adversas do meio que impedem a administração oral destas moléculas. Neste contexto, os sistemas de transporte mais estudados, para a encapsulação destas macromoléculas, são as nanopartículas poliméricas e dentro destas são preferidos os sistemas biodegradáveis. A encapsulação irá proteger o antigénio do meio ácido e rico em enzimas proteolíticas como é o tubo digestivo. Para além das vantagens apontadas, acresce ainda referir que um sistema de transporte polimérico permite uma cedência gradual das moléculas activas, prolongando o seu efeito no organismo e contribuindo assim para a simplificação dos esquemas posológicos. Por outro lado, estes sistemas contribuem igualmente para a simplificação da logística de produção, armazenamento e distribuição de vacinas. Um dos sistemas que tem sido estudado é o de bioadesivos de libertação de fármacos (BDDS- bioadhesive drug delivery system). Os Tecnologistas estão confiantes que este novo conceito poderá contornar as dificuldades relacionadas com a libertação oral de peptídeos e análogos de peptídeos. Os BDDS são produzidos com a finalidade de se fixarem ao revestimento mucoso do tracto gastrointestinal. Desta forma, este sistema deverá exercer uma influência positiva na absorção dos fármacos que transportam. Essa influência deverá fazer-se por vários mecanismos: - prolongamento do tempo de residência no local de absorção do fármaco, com vista à redução da frequência de administração. - Intensificação do contacto com a barreira epitelial da mucosa subjacente, com vista ao incremento do transporte através do epitélio. - Pensa-se que alguns polímeros mucoadesivos têm a capacidade de modular a permeabilidade dos tecidos epiteliais, actuando ao nível das junções das células do epitélio (tight junctions). - Pensa-se igualmente, que alguns polímeros mucoadesivos podem actuar como inibidores de enzimas proteolíticas. Considerações finais: neste trabalho foi apresentado um novo sistema de libertação constituído por nanopartículas poliméricas. As nanopartículas são constituídas por um núcleo de quitosano onde foi posteriormente adsorvido o antigénio e finalmente revestido com alginato de sódio. O método desenvolvido permite encapsular, com elevada eficiência, antigénios do tipo proteico em condições reconhecidamente não agressivas, minimizando assim a possibilidade de perda de acção biológica por parte da vacina. As nanopartículas revestidas mostraram ter um efeito adjuvante relativamente à vacina da hepatite B quando administradas pela via subcutânea. A adição do imunopotenciador CpG ODN à suspensão das nanopartículas, contendo o antigénio da hepatite, permitiu modificar o tipo de resposta imune de Th2 para uma resposta mista Th1/Th2, mais adequada no caso do vírus da hepatite B. A administração, através das mucosas oral e nasal, da vacina da hepatite B encapsulada nas nanopartículas de quitosano revestidas permitiu confirmar a opinião de muitos especialistas na área da vacinologia, que defendem que não será suficiente a inclusão do antigénio em sistemas de libertação de nanopartículas, principalmente quando se trata de um antigénio fraco. Para se obter uma resposta imunológica adequada, para além da encapsulação do antigénio, vai ser ainda necessário adicionar um imunopotenciador. De facto, os melhores resultados foram obtidos com formulações que continham na sua composição o CpG ODN. Para finalizar, o sistema nanoparticular desenvolvido mostrou ser igualmente útil para a encapsulação do imunopotenciador em formulações orais. Em contraste, na mucosa nasal, o imunopotenciador produziu melhores resultados quando foi administrado em solução, pelo que a futura utilização destas nanopartículas para a encapsulação de moléculas que demonstrem uma elevada afinidade para o quitosano, como o caso do CpGODN, estará condicionada a uma optimização conveniente destas nanopartículas. As nanopartículas de quitosano, revestidas com alginato provaram ter um efeito adjuvante com o antigénio da hepatite B pela via subcutânea. Por conseguinte, os próximos estudos serão feitos com o objectivo de avaliar se o sistema nanopartícular poderá substituir, com vantagem, o actual adjuvante (compostos de alumínio), da vacina da hepatite B. Para finalizar, o efeito adjuvante, observado para a vacina da hepatite B, deverá ser avaliado com outras vacinas, de preferência mais fortes, não só pela via subcutânea mas também através das mucosas oral e nasal.
Este trabalho foi parcialmente realizado na qualidade de bolseiro da Fundação para a Ciência e Tecnologia no âmbito do POCTI – Formar e Qualificar – Medida 1.1 (referência SFRH/BD/5327/2001).
Bento, Dulce Marisa Ferreira. "Association of compound 48/80 with chitosan based nanoparticles: designing a novel prototypic delivery system for nasal vaccination." Doctoral thesis, 2017. http://hdl.handle.net/10316/32137.
Повний текст джерелаA vacinação é considerada como uma das medidas de saúde publica de controlo de doenças infetocontagiosas mais eficazes na civilização moderna. Os programas de imunização em larga escala diminuíram significativamente a morbilidade e mortalidade atribuídas às doenças infeciosas. A melhoria das vacinas atuais, e o desenvolvimento de vacinas para doenças contra as quais ainda não existem vacinas eficazes, são linhas de investigação de grande importância e com grande impacto na saúde pública e na sociedade. Particularmente, o desenvolvimento de vacinas para administração pelas mucosas será altamente desejável dado que, para além de permitir uma mais fácil administração, permitirá conferir proteção imunológica específica no local de entrada dos patogéneos. A colocação no mercado deste tipo de vacinas tem sido adiada devido à falta de adjuvantes seguros e eficazes para estas vias de administração. O objetivo deste projeto foi desenvolver um novo sistema de entrega de antigénios, com função adjuvante, para vacinação nasal. Este sistema de entrega é composto por dois adjuvantes para as mucosas, os quais, individualmente, em ensaios pré-clínicos, já mostraram ser muito promissores: nanopartículas de quitosano e um ativador de mastócitos, o composto 48/80 (C48/80). Esta é a primeira vez que é descrita a combinação do C48/80 com nanopartículas com o objetivo de desenvolver uma melhor formulação adjuvante para vacinas. Foram desenvolvidos dois sistemas de entrega, tendo por base o quitosano para a formação de nanopartículas, e nas quais se encapsulou o C48/80: Quitosano-C48/80 NP (Chi-C48/80 NP) e Quitosano/Alginato-C48/80 NP (Chi/Alg-C48/80 NP). As duas formulações foram caracterizadas e avaliadas in vitro. À posteriori, estudos in vivo avaliaram o seu potencial como adjuvantes para vacinas nasais. Para auxiliar no desenvolvimento das nanopartículas carregadas com C48/80, foi desenvolvido um método colorimétrico com deteção por espetrofotometria UV-Vis para a quantificação do C48/80. Este método foi validado de acordo com as recomendações das normas ICH para os seguintes parâmetros: especificidade, gama de trabalho e linearidade, exatidão, precisão e limites de deteção e de quantificação. As nanopartículas desenvolvidas no decurso deste projeto, Chi-C48/80 NP e Chi/Alg-C48/80 NP apresentaram um tamanho médio de 501 nm e 564 nm, respetivamente, e ambas apresentaram um potencial zeta positivo. A eficácia de carregamento do C48/80 foi 19 % para as Chi-C48/80 NP e 30 % para as Chi/Alg-C48/80 NP. Estudos de citotoxicidade demonstraram que a incorporação do C48/80 nos sistemas de entrega diminui a toxicidade do imunopotenciador. Estudos in vitro de internalização revelaram que as Chi-C48/80 NP foram internalizadas por células apresentadoras de antigénio mais eficientemente que as Chi/Alg-C48/80 NP. A capacidade das nanopartículas desenvolvidas para ativarem mastócitos foi também testada in vitro usando o ensaio de libertação de β-hexosaminidase. Os resultados demonstraram que a associação do C48/80 com as Chi NP, mas não com as Chi/Alg NP, resultou numa maior ativação de mastócitos quando comparado com o C48/80 em solução. Para avaliar se as particulas mucoadesivas, à base de quitosano, conseguiam aumentar o tempo de residência do antigénio na cavidade nasal, foi realizado um estudo in vivo de clearance nasal. Com esse objetivo foi usada ovalbumina marcada com fluorescência, adsorvida às nanopartículas. Neste estudo as Chi-C48/80 NP superaram novamente as Chi/Alg-C48/80 NP aumentando significativamente o tempo de residência do antigénio na cavidade nasal. A aptidão das nanopartículas desenvolvidas para potenciarem uma resposta imune, foi avaliada em murganhos C57BL/6 usando a imunização nasal com o antigénio protetor (PA) do B. anthracis como sistema modelo. A imunização usando as Chi-C48/80 NP como adjuvante induziu títulos elevados de anticorpos neutralizantes anti-PA no soro e títulos de anticorpos IgG2c anti-PA mais elevados do que as Chi/Alg-C48/80 NP. A incorporação do C48/80 nas Chi NP também promoveu uma imunidade nas mucosas melhor que a induzida por todos os outros grupos testados. Estes estudos de vacinação demonstraram que as Chi-C48/80 NP exibiram um desempenho melhor como adjuvante para a mucosa nasal que as Chi/Alg-C48/80 NP. Além disso, um estudo de dose-resposta revelou que as Chi-C48/80 NP permitiram diminuir seis vezes a dose de antigénio usada, sem afetar os títulos de anticorpos IgG específicos e neutralizantes. Estes resultados sugerem que esta inovadora combinação de adjuvantes, Chi NP com C48/80, tem potencial para diminuir a dose de antigénio necessário a incluir numa formulação comercial da vacina. De um modo geral, os resultados obtidos com este projeto demonstram que a combinação de nanopartículas de quitosano com um ativador de mastócitos é uma estratégia promissora para a imunização nasal, induzindo uma resposta imune potente, tanto sistemicamente como nas mucosas.
Vaccination is considered one of the greatest medical achievements of modern civilization and large scale immunization programs greatly reduced the global burden of infectious diseases. Therefore, improvement of current vaccines and development of vaccines against diseases for which successful vaccines are not currently available would bring huge benefits for public health and for the society. The development of mucosal vaccines would be highly desirable since it would provide protection at the local of entry of pathogens. However, the development of mucosal vaccination strategies has been delayed for the lack of effective and safe mucosal adjuvants. The objective of this project was to develop a novel prototypic delivery system for nasal vaccination composed by two highly promising mucosal adjuvant candidates: chitosan nanoparticles and the mast cell activator compound 48/80 (C48/80). This is the first time that the combination of C48/80 with nanoparticles in order to develop an improved adjuvant formulation is described. Two different C48/80 loaded chitosan-based delivery systems were developed: Chitosan-C48/80 NP (Chi-C48/80 NP) and Chitosan/Alginate-C48/80 NP (Chi/Alg-C48/80 NP). The two C48/80 loaded delivery systems were characterized and evaluated in vitro. Subsequently, in vivo studies assessed their potential as nasal adjuvants. To support the development of C48/80 loaded nanoparticles, a UV-Vis spectrophotometric method for quantification of C48/80 was developed. This method was validated according to the recommendations of ICH Guidelines for specificity, linearity, range, accuracy, precision and detection and quantification limits. Chi-C48/80 NP and Chi/Alg-C48/80 NP had a mean size of 501 nm and 564 nm, respectively, and were both positively charged. Loading efficacy of C48/80 was 19 % for Chi-C48/80 NP and 30 % for Chi/Alg-C48/80 NP. Cytotoxicity studies performed in two different cell types showed that incorporation of C48/80 in both formulations resulted in a decreased toxicity of the immunopotentiator compared with C48/80 in solution. In vitro uptake studies showed that Chi-C48/80 NP were more efficiently internalized by antigen presenting cells than Chi/Alg-C48/80 NP. The ability of the developed nanoparticles to activate mast cells was tested in vitro using the β-hexosaminidase release assay. Results demonstrated that association of C48/80 with Chi NP but not with Chi/Alg NP enhanced mast cell activation when compared with C48/80 in solution. To see if the mucoadhesive chitosan-based nanoparticles could increase the residence time of an antigen, an in vivo nasal clearance study of fluorescently labelled ovalbumin loaded on nanoparticles was performed. Once again, Chi-C48/80 NP outperformed Chi/Alg-C48/80 NP significantly increasing ovalbumin residence time in the nasal cavity. Both delivery systems, Chi-C48/80 NP and Chi/Alg NP were then compared for their ability to induce antigen-specific serum IgG, mucosal IgA and serum lethal toxin-neutralizing antibody responses in C57BL/6 mice using nasal immunization with anthrax recombinant protective antigen (PA) as a model system. Nasal immunization with Chi-C48/80 NP as adjuvant elicited high levels of serum anti-PA neutralizing antibodies and higher antigen-specific IgG2c than Chi/Alg-C48/80 NP. The incorporation of C48/80 within Chi NP also promoted a mucosal immunity greater than all the other adjuvanted groups tested. These vaccination studies showed that Chi-C48/80 NP displayed a better performance as nasal adjuvant than Chi/Alg-C48/80 NP. Additionally, an antigen dose-response study showed that Chi-C48/80 NPs allowed a 6-fold decrease of the antigen dose without affecting the levels of specific IgG titers and its neutralizing ability. These results suggest the potential of this novel adjuvant combination to decrease the antigen dose required for vaccination. Overall, the findings of this project show that the combination of a mast cell activator with chitosan nanoparticles is a promising strategy for nasal immunization inducing potent systemic and mucosal immune responses.
Thapa, Manoj. "Protective mucosal immunity elicited by intranasal DNA vaccination expressing HA1 of equine-2 influenza virus." 2005. http://digital.library.okstate.edu/etd/umi-okstate-1451.pdf.
Повний текст джерелаRolon, Ariel. "Salmonella vaccination studies in breeders and their progeny relating humoral and mucosal immunity with resistance to challenge /." 2005. http://purl.galileo.usg.edu/uga%5Fetd/rolon%5Fariel%5F200505%5Fphd.
Повний текст джерелаHuang, Ching-Feng, and 黃清峰. "Effect of sublingual vaccination on mucosal immunity, allergic prevention and bacterial resistance in adult and newborn mice." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/86732071878443489686.
Повний текст джерела國防醫學院
醫學科學研究所
96
Current clinical vaccination has included different pathways, including intravenous, intradermal, subcutaneous and intramuscular routes. The efficacy of subcutaneous immunotherapy for allergic diseases is well documented, but the possibility of fatal anaphylaxis can not be excluded. The efficacy and safety of sublingual immunotherapy has been also confirmed in recent years. In fact, mucosal immunity plays a crucial role to counteract aeroallergens and mucosal pathogens at their first encounter. SIgA is the first line of mucosal defense. Its effects to minimize mucosal permeability of allergens and invasion of bacterial pathogens have been termed as “immune exclusion”. Therefore, induction of mucosal immunity is important to prevent mucosal infections and allergic reactions. Vaccination with protein vaccines and adjuvants such as cholera toxin and CpG oligodeoxynucleotides (CpG) can effectively trigger systemic immunity. Denaturation of proteins can abrogate allergenicity and oral tolerogenicity, but there is so far no study of the effect of sublingual vaccination with a denatured protein. Adult BALB/c mice were thus sublingually vaccinated with native OVA or its denatured form CM-OVA. Sublingual vaccination together with adjuvant CpG enhanced saliva specific SIgA antibody responses and systemic Th1 responses, including higher IFN-r production by spleen and cervical lymph node (CLN) cells, higher serum specific IgG2a and lower serum specific IgE antibody responses. In contrast, sublingual vaccination together with adjuvant CT increased saliva specific SIgA antibody responses and systemic Th2 responses, including higher IL-4, IL-5 and IL-6 production by spleen and CLN cells, and enhanced serum specific IgG1 antibody responses. However, the effect of sublingual vaccination on previously sensitized mice had not been studied. Those sublingually treated with OVA or CM-OVA, plus either CT or CpG, stimulated saliva SIgA antibody responses. The mice sublingually vaccinated together with adjuvant CpG had much enhanced serum specific IgG2a but markedly suppressed IgE antibody responses. Vaccination with strong adjuvant may be more helpful for newborns to overcome their immune immaturity. However, there is no study of the effect of sublingual vaccination on newborns. Salmonella enteritidis is a common intestinal pathogen. Symptomatic Salmonella infections range from mild enteritis to severe life-threatening sepsis. Most experimental vaccines against Salmonella have been applied by injection. It will be better to try other routes to have no pains. Newborn mice were sublingually vaccinated for the first time. Neonatal sublingual vaccination with sonicated Salmonella proteins (SSP) and adjuvant CpG enhanced saliva specific SIgA antibody responses and systemic Th1 responses, including higher IFN-r production by spleen and CLN cells, and increased serum specific IgG2a antibody responses. In contrast, neonatal sublingual vaccination with SSP and CT increased saliva specific SIgA antibody responses and systemic Th2 responses, including enhanced IL-4, IL-5 and IL-6 production by spleen and CLN cells, and higher serum specific IgG1 antibody responses. After further challenge with live Salmonella enteritidis, only the adult mice receiving neonatal sublingual vaccination with SSP and adjuvant CpG or CT had effective prophylaxis against necrotic enteritis, and the best survival rate. Sublingual vaccination with antigens and mucosal adjuvants can induce systemic and mucosal immunity and further prevent allergic and infectious reactions in adult and newborn mice. It is a simple and easy way to develop mucosal vaccines for prophylaxis and immunotherapy.
Behl, Michelle 1983. "Role of Vaccination in the Control of Turkey Coccidiosis: Vaccine Associated Oocyst Shedding, Lesions, and Mucosal Gene Expression." Thesis, 2011. http://hdl.handle.net/1969.1/149207.
Повний текст джерелаMannam, Praveen. "Immune response and protection against Streptococcus pyogenes after vaccination with Lactococcus lactis that expresses conserved region of M6 protein." Thesis, 2003. http://hdl.handle.net/1957/30816.
Повний текст джерелаGraduation date: 2004
Lebre, Filipa Raquel Maia Fontes. "Development of chitosan-based nanoparticles for nasal immunization against hepatitis B." Doctoral thesis, 2017. http://hdl.handle.net/10316/41058.
Повний текст джерелаVaccines are one of medicine greatest achievements, reducing the incidence of infectious diseases and eradicating otherwise fatal diseases worldwide. However, hepatitis B virus (HBV) infection is still a major global health concern and the most common cause of chronic liver disease and mortality from hepatocellular carcinoma. New generation vaccines are needed in order to overcome the limitations of the current HBV vaccines in the market. In this regard, mucosal immunization constitutes an attractive alternative to the available parenteral vaccine, especially in developing countries, since it would be best suited for mass immunization and would provide protection at the pathogen entry site. The main objective of this thesis was to develop the next generation of HBV vaccines exploiting the immunomodulatory and mucoadhesive properties of chitosan-based delivery nanoparticles. This strategy would improve not only mucosal- and cell-mediated immunity, but would also allow the vaccine to be efficiently administered through the nasal mucosa. To achieve this goal, two different approaches were developed and tested. First, a novel prototypic system combining two well-established immunopotentiators, chitosan and aluminium salts, was produced to deliver hepatitis B surface antigen (HBsAg). Adjuvant combination has been considered a promising strategy to boost immunogenicity. The second approach involved the generation of a gene delivery system consisting of complexes of human serum albumin (HSA)-loaded chitosan nanoparticles with DNA (HSA-CH NP/DNA) encoding HBsAg. The two delivery systems were characterized and evaluated, both in vitro and in vivo. In order to fulfill the main goal, we established a detailed methodology to easily obtain large quantities of endotoxin-free chitosan without modifying its immunomodulatory properties. Bacterial endotoxins content was assessed according to the recommendations of the International Council for Harmonization (ICH) guideline and validated with in vitro data. Chitosan-aluminium nanoparticles (CH-Al NPs) were prepared using a nanoprecipitation technique; the optimal formulation exhibited a mean diameter of 280 nm and a positive surface charge, showing no cytotoxic effects in two different cell lines and in a primary culture of splenocytes, in the dose used for in vivo studies. In vitro uptake studies showed that CH-Al NPs were efficiently internalized by epithelial cells, demonstrating potential as a delivery system for a wide range of model antigens. Immunization studies showed that mice subcutaneously immunized with HBsAg adjuvanted with CH NPs displayed enhanced humoral and cellular immune responses. To understand the underlying mechanisms of adjuvanticity of CH-Al NPs, the ability of CH-Al NPs to promote dendritic cell (DC) activation and their potential to stimulate innate and adaptive immune responses was assessed. Results were correlated to those obtained with chitosan in solution (CH sol.) and conventional chitosan particles (CH-Na NPs). All the formulations were capable of modulating Toll-like receptor (TLR)-9 agonist, CpG, induced cytokine secretion in bone-marrow derived dendritic cells (BMDCs) and induced DC maturation in the absence of cytokine production. After intraperitoneal (I.P.) injection, CH-Al NPs were capable of generating a local immune response comparable to that elicited by the vaccine adjuvant alum, with recruitment of neutrophils and eosinophils and concomitant disappearance of resident macrophages and mast cells. After vaccination with CH-Al NPs in combination with HBsAg, mice developed high antigen-specific immunoglobulin G (IgG) titers in the serum, as well as in nasal and vaginal washes, generating an overall improved immune profile in comparison to the commercially available vaccine Engerix-B. In the second approach, a DNA vaccine was developed in which a plasmid coding for the HBsAg was adsorbed on the surface of the HSA-loaded CH NPs. The presence of HSA enhanced transfection activity and facilitated DNA release from the complex by weakening the interaction between positively charged nanoparticles and negatively charged plasmid DNA (pDNA). To assess in vivo the value of the developed formulation, immunization studies were conducted. Nasal immunization with HSA-CH NP/DNA complexes elicited high levels of serum anti-HBsAg IgG and antigen-specific IgA in nasal and vaginal secretions, while no systemic or mucosal responses were detected after immunization with DNA alone. These results confirm the ability of this novel delivery system to generate a mucosal immune response, making it a valuable adjuvant for nasal vaccination against HBV. Overall, our findings add to our knowledge of the mechanism of action of chitosan-based formulations and illustrate that proper design is vital in order to generate an effective adjuvant for HBV vaccines, capable of driving mucosal immune responses in addition to potent humoral and cell-mediated immunity.
As vacinas são uma das maiores conquistas da medicina, reduzindo a incidência de doenças infeciosas e erradicando mundialmente doenças que outrora seriam fatais. Apesar de existir no mercado uma vacina profilática contra a hepatite B, a infeção pelo vírus da hepatite B (VHB) continua a ser um dos principais problemas de saúde pública e a causa mais comum de doença hepática crónica e mortalidade por carcinoma hepatocelular. É por isso necessário uma nova geração de vacinas que ultrapassem as limitações das vacinas contra o VHB atualmente no mercado. Nesse sentido, a imunização pelas mucosas constitui uma alternativa apelativa à vacina parentérica disponível, especialmente nos países em desenvolvimento, uma vez que seria mais adequada para imunização em massa e proporcionaria proteção no local de entrada do patogéneo, nomeadamente no caso de uma doença sexualmente transmitida. Neste sentido, o principal objetivo desta tese consiste em desenvolver a próxima geração de vacinas contra o VHB explorando as propriedades imunomoduladoras e mucoadesivas de nanopartículas à base de quitosano. Esta nova vacina melhoraria não só a imunidade ao nível das mucosas e a mediada por células, como permitiria que a vacina fosse administrada de forma eficiente através da mucosa nasal. Para atingir este objetivo, duas estratégias diferentes foram desenvolvidas e testadas. Primeiro, foi otimizado um novo sistema protótipico de liberação do antigénio de superfície do vírus da hepatite B (HBsAg), combinando dois imunopotenciadores bem estabelecidos, o quitosano e os sais de alumínio, uma vez que a combinação de adjuvantes tem sido considerada uma estratégia promissora para potenciar a resposta imunológica; segundo, foram também desenvolvidos complexos de nanopartículas de quitosano carregados com albumina de soro humano (HSA) e complexados com ADN (HSACH NP/ADN), usados para estimular a resposta imune sistémica e nas mucosas após administração intranasal. Os dois sistemas de libertação de moléculas ativas foram caracterizados e avaliados quer in vitro, quer in vivo. Para cumprir o objetivo principal, estabelecemos uma metodologia detalhada de modo a obter facilmente quitosano livre de endotoxinas, sem comprometer as suas propriedades bioquímicas. O conteúdo das endotoxinas bacterianas foi avaliado em conformidade com as recomendações da diretiva do Conselho Internacional de Harmonização (ICH) e validado com dados obtidos em estudos in vitro. As nanopartículas de quitosano alumínio (CH-Al NPs) foram preparadas utilizando uma técnica de nanoprecipitação; a formulação otimizada exibiu um diâmetro médio de 280 nm e uma carga de superfície positiva, não apresentando efeitos citotóxicos em duas linhas celulares diferentes e numa cultura primária de esplenócitos, para a dose utilizada posteriormente em estudos de imunização. Estudos de internalização in vitro demonstraram que as CH-Al NPs foram eficientemente internalizadas por células epiteliais exibindo potencial como sistema de libertação para uma ampla gama de antigénios modelo. Estudos in vivo mostraram que murganhos imunizados pela via subcutânea com HBsAg coadjuvado com CH NP apresentaram uma melhor resposta imune humoral e celular quando comparado com o grupo de murganhos vacinados apenas com o antigénio. Para entender os mecanismos subjacentes de adjuvanticidade das CH-Al NPs, avaliou-se a sua capacidade para promover a ativação de células dendríticas (DC), e o seu potencial para estimular respostas imunes inatas e adaptativas. Os resultados foram correlacionados com os obtidos com quitosano em solução (CH sol.) e partículas de quitosano convencionais (CH-Na NP). Todas as formulações foram capazes de modular a secreção de citoquinas induzida por agonistas dos recetores tipo-Toll (TLR)-9, CpG, em células dendríticas derivadas da medula óssea de murganho (BMDCs) e induziram a maturação de DC na ausência de produção de citoquinas. Após a injeção intraperitoneal (I.P.), as CH-Al NPs foram capazes de gerar uma resposta imunitária local comparável à evocada por sais de alumínio usado com adjuvantes em vacina que se caracterizou por recrutar neutrófilos e eosinófilos e por um desaparecimento de macrófagos e mastócitos. Após a vacinação com CH-Al NP pela via subcutânea em combinação com HBsAg, os murganhos desenvolveram títulos elevados de anticorpos IgG anti-HBsAg no soro, bem como nas lavagens nasais e vaginais, gerando um perfil imunológico melhorado em comparação com a vacina comercialmente disponível, Engerix-B. Na segunda abordagem foi desenvolvida uma vacina de ADN na qual um plasmídeo que codifica o HBsAg foi adsorvido na superfície das CH-NPs carregadas com HSA. A presença de HSA aumentou a atividade de transfecção e facilitou a libertação de ADN a partir do complexo, por enfraquecer a interação entre nanopartículas positivamente carregadas e o ADN carregado negativamente. Para avaliar o potencial da formulação desenvolvida foram conduzidos estudos in vivo. A imunização com complexos HSA-CH NP/ADN originou níveis elevados de anticorpos IgG anti-HBsAg e anticorpos IgA específicos contra o HBsAg nas secreções nasais e vaginais, enquanto não foram detetadas respostas sistémicas ou nas mucosas após imunização com ADN sozinho. Estes resultados demonstram o potencial deste novo sistema de administração em gerar uma resposta imune nas mucosas, tornando-o num adjuvante promissor para a vacinação nasal contra o HBV. De modo geral, os resultados obtidos melhoram o nosso conhecimento de formulações à base de quitosano e demonstram que o design apropriado é vital para a formular um adjuvante eficaz para vacinas contra o HBV, capaz de produzir respostas imune ao nível das mucosas além de potenciar imunidade humoral e celular.