3,353 research outputs found
A vaccine against Alzheimer's disease: anything left but faith?
No full textINTRODUCTION
Alzheimer's disease looms as a profound and growing threat to future human health. The disease is thought to be primarily driven by aberrant proteolysis of the amyloid precursor protein and amyloid beta (Aβ) plaque deposition. Areas covered: We provide an overview of the molecular pathology that leads to an increase in Aβ peptide accumulation, of the mechanism of action for antibody mediated therapies and of the therapeutic vaccines that target Aβ under development. We also discuss the rationale for using vaccines in the early stages of the disease. Expert opinion: The major components of β-amyloid plaques are Aβ and Aβ peptides derived from the Amyloid precursor protein (APP). Reducing these plaques by means of passive or active vaccination against Aβ-peptides has been a long-running endeavour but with disappointing results as the impact on disease progression has been minimal. The data gathered to date could suggest that antibodies do not work, mainly because the studies have not been performed in an optimal fashion. The emerging views are that patients should be treated earlier, ideally in the prodromal or symptom free stage, antibody levels have to be high and the correct epitope must be targeted. More clinical trials to fully explore the potential of vaccines are therefore warranted
Special Issue "Virus-Like Particle Vaccines".
Get PDFVirus-like particles (VLPs) have become a key tool for vaccine developers and manufacturers [...
Immunogenicity and Immunodominance in Antibody Responses.
No full textA large number of vaccines exist that control many of the most important infectious diseases. Despite these successes, there remain many pathogens without effective prophylactic vaccines. Notwithstanding strong difference in the biology of these infectious agents, there exist common problems in vaccine design. Many infectious agents have highly variable surface antigens and/or unusually high antibody levels are required for protection. Such high variability may be addressed by using conserved epitopes and these are, however, usually difficult to display with the right conformation in an immunogenic fashion. Exceptionally high antibody titers may be achieved using life vectors or virus-like display of the epitopes. Hence, an important goal in modern vaccinology is to induce high antibody responses against fragile antigens
Musikstädte as real and imaginary soundscapes: urban musical images as literary motifs in twentieth-century German modernism
No full textPhDThis study examines German literary images of musical life as part of the wider sound identity of the modern German city at the turn of the twentieth century. Focussing on a forty-year period from 1890 to 1930, synonymous with the emergence of the modern German metropolis as an aesthetic object, the project assesses, compares and contrasts how musical life in the Musikstädte was perceived and portrayed by writers in an increasingly noisy urban environment. How does urban musical life influence and condition city writings? What are the differences and similarities between the writings on various musical cities? Can an urban textual sound identity be derived from these differences and similarities? The approach employed to answer these questions is a new, cross-disciplinary one to urban sound in literature, moving beyond reading the key sounds of the urban soundscape using urban musicology, sensorial anthropology and cultural poetics towards a literary contextualisation of the urban aural experience.
The literary motifs of the symphony, the gramophone and urban noise are put under the spotlight through the analysis of a wide range of modernist works by authors who have a special relationship with music. At the centre of this analysis are the Kaffeehausliteratur authors Hermann Bahr, Alfred Polgar and Peter Altenberg, the then Munich-based author Thomas Mann and the lesser known René Schickele. The analysis of these particular works is framed in the music-geographical context of the Musikstadt and literary underpinnings of this topos, ranging from Ingeborg Bachmann to Hans Mayer and, once again, Thomas Mann. In analysing these texts, the methodological approach devised by Strohm, who identifies the blending of a range of urban sounds as a definition of urban space and identity, is applied. His ideas combine historical literary
analysis, musical history and urban sociology. They are rarely used in the analysis of the auditory environment.Arts and Humanities Research Council
Westfield TrustWestfield Trust Studentship
Arts and Humanities Reseach Council (AHRC
Vaccine against peanut allergy based on engineered Virus-Like-Particles displaying single major peanut allergens
Get PDFBackground
Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial and economical burden for affected patients. A causal, safe and effective therapy is not available.
Objective
We aimed to develop an immunogenic, protective and non-reactogenic vaccine candidate against peanut allergy based on Virus-like Particles (VLPs) coupled to single peanut allergens.
Methods
To generate vaccine candidates, extracts of roasted peanut (Ara R) or the single allergens Ara h 1 or Ara h 2 were coupled to immunologically optimized Cucumber Mosaic Virus-derived VLPs (CuMVtt). BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to Alum. Immunotherapy consisted of one single subcutaneous injection of CuMVtt coupled to Ara R, Ara h 1 or Ara h 2.
Results
The vaccines CuMVtt-Ara R, CuMVtt-Ara h 1 and CuMVtt-Ara h 2 protected peanut sensitized mice against anaphylaxis after i.v. challenge with the whole peanut extract. Vaccines did not cause allergic reactions in sensitized mice. CuMVtt-Ara h 1 was able to induce specific IgG antibodies, diminished local reactions after skin-prick-tests and reduced the infiltration of the gastrointestinal tract by eosinophils and mast cells after oral challenge with peanut. The ability of CuMVtt-Ara h 1 to protect against challenge with the whole extract was mediated by IgG, as shown via passive IgG transfer. FcγRIIb was required for protection, indicating that immune-complexes with single allergens were able to block the allergic response against the whole extract, consisting of a complex allergen mixture.
Conclusion
Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel and safe therapy against peanut allergy
Virus-like particle vaccinology, from bench to bedside
Get PDFVirus-like particles (VLPs) have become key tools in biology, medicine and even engineering. After their initial use to resolve viral structures at the atomic level, VLPs were rapidly harnessed to develop antiviral vaccines followed by their use as display platforms to generate any kind of vaccine. Most recently, VLPs have been employed as nanomachines to deliver pharmaceutically active products to specific sites and into specific cells in the body. Here, we focus on the use of VLPs for the development of vaccines with broad fields of indications ranging from classical vaccines against viruses to therapeutic vaccines against chronic inflammation, pain, allergy and cancer. In this review, we take a walk through time, starting with the latest developments in experimental preclinical VLP-based vaccines and ending with marketed vaccines, which earn billions of dollars every year, paving the way for the next wave of prophylactic and therapeutic vaccines already visible on the horizon
COVID-19: Mechanisms of Vaccination and Immunity.
Get PDFVaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world's population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy
Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.
Get PDFBACKGROUND
Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses.
OBJECTIVE
Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study.
METHODS
The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMV ) using a semi-crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 μg of eIL-5-CuMV without adjuvant.
RESULTS
The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms.
CONCLUSION
Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans
Successful Allergen-Specific Immunotherapy: Induction of Unresponsiveness by 'Vaccination'.
Get PDFThe mechanisms of action of allergen-specific immunotherapy (AIT) are often referred to as the induction of 'tolerance'. However, immunological 'tolerance' is defined as an alteration in the function or composition of immune cells. For AIT, this is not always the case, because it can also induce allergen-specific IgG antibodies that block allergic responses. To include all possible mechanisms that may mediate successful AIT, it is advantageous to use the scientific term 'unresponsiveness' instead of 'tolerance'. In praxis, the term 'vaccination' is also appropriate, as AIT medications are specialized vaccines
Generation of a virus-like particles based vaccine against IgE.
Get PDFBACKGROUND
Anti-IgE immunotherapy with monoclonal antibodies represents a breakthrough in treatment of severe allergic diseases. However, drawbacks such as short half-life and high price are not negligible. Our objective is to develop an anti-IgE vaccine based on virus-like particles (VLPs) which can induce long-lasting neutralizing IgG anti-IgE antibodies reducing allergic responses without causing intrinsic mast cell activation due to IgE cross-linking.
METHODS
The vaccines were made by chemically coupling three synthetic mouse IgE-Fc fragments to plant-derived immunologically optimized CuMVTT VLPs. The immunogenicity of the vaccines was tested by immunizing naive or allergic mice either with the coupled vaccines or the VLP control followed by systemic or local allergen challenge.
RESULTS
Mice immunized with the vaccines exhibited high titers of anti-IgE antibodies in the sera and high levels of anti-IgE secreting plasma cells in lymphoid organs. Moreover, free IgE in serum were reduced by the induced anti-IgE antibodies; therefore, less IgE was bound to FcεRI on the surface of basophils. In line with these reduced IgE levels on effector cells after vaccination, immunized mice were protected from challenge with allergens. Importantly, despite presence of anti-IgE antibodies, no signs of acute or chronic allergic response were seen in immunized allergic mice.
CONCLUSION
The generated vaccines can effectively induce anti-IgE antibodies that did not cause allergic responses in sensitized mice but were able to decrease the level of free and cell bound IgE and protected sensitized animals from allergic responses upon allergen challenge
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