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Solna, Sweden

Grundstrom J.,Karolinska University Hospital | Neimert-Andersson T.,Karolinska University Hospital | Kemi C.,National Institute of Environmental Medicine | Kemi C.,Karolinska Institutet | And 5 more authors.
International Archives of Allergy and Immunology | Year: 2012

Background: Allergen-specific immunotherapy (SIT) is currently the only curative treatment for allergy but the treatment needs to be improved. We hypothesize that covalent coupling of immunomodulating vitamin D3 to the major cat allergen Fel d 1 can enhance the beneficial effects of SIT to cat allergy. Methods: We treated mice sensitized to Fel d 1 with subcutaneous injections of two doses of recombinant Fel d 1 coupled to 1α,25-dihydroxyvitamin D3 (rFel d 1:VD3) and compared to treatment with the same doses of rFel d 1 in a mouse model for cat allergy. Airway hyperresponsiveness (AHR), cytokines and cells in bronchoalveolar lavage (BAL), in vitro activation of splenocytes to rFel d 1, and Fel d 1-specific immunoglobulins were evaluated. Results: Treatment with both doses of rFel d 1:VD3 decreased AHR, cellular influx and Th2 cytokines in BAL compared to untreated mice. High-and low-dose rFel d 1 treatment also decreased AHR and BAL Th2 cytokines, with less decrease for the low-dose treatment. Importantly, the total number of cells and eosinophils in BAL was markedly reduced at both high-and low-dose rFel d 1:VD3 compared to treatment with rFel d 1 alone. Finally, treatment with both rFel d 1 and rFel d 1:VD3 induced Fel d 1-specific serum IgG. Conclusion: Our results indicate a beneficial therapeutic effect of rFel d 1:VD3 on airway inflammation, AHR and rFel d 1-specific immune responses and thus suggest that this novel immunomodulatory candidate may improve both the efficacy and safety of SIT. © 2011 S. Karger AG, Basel. Source


Patent
Viscogel Ab | Date: 2011-04-15

This invention provides a composition comprising: (i) a chitosan hydrogel comprising cross-linked chitosan and water; and (ii) a liquid dispersed in the hydrogel.


Neimert-Andersson T.,Viscogel AB | Neimert-Andersson T.,Karolinska Institutet | Binnmyr J.,Viscogel AB | Binnmyr J.,Karolinska Institutet | And 15 more authors.
Vaccine | Year: 2014

ViscoGel, a chitosan-based hydrogel, has earlier been shown to improve humoral and cell-mediated immune responses in mice. In this study, a Phase I/IIa clinical trial was conducted to primarily evaluate safety and secondarily to study the effects of ViscoGel in combination with a model vaccine, Act-HIB to Haemophilus influenzae type b, administered as a single intramuscular injection. Healthy volunteers of both sexes, ages 22-50 and not previously vaccinated to HIB, were recruited. The trial had two phases. In Phase A, three ascending dose levels of ViscoGel (25, 50 and 75. mg) were evaluated for safety in 3. ×. 10 subjects. Phase B had a single-blind, randomised, parallel-group design evaluating safety and efficacy in five groups, 20 subjects/group, comparing vaccination with 0.2. μg or 2. μg Act-HIB alone or combined with ViscoGel (50. mg) and one group receiving the standard Act-HIB dose (10. μg). No safety or tolerability concerns were identified. Local, transient reactions at the injection site were the most common adverse events. These were more frequent in groups receiving Act-HIB. +. ViscoGel, while other AEs were recorded at similar frequency in Act-HIB and Act-HIB. +. ViscoGel groups. Efficacy was evaluated by measuring serum anti-HIB antibodies and cellular responses in peripheral blood mononuclear cells (PBMC). There was a large variation in baseline anti-HIB antibody titres and no adjuvant effect was observed on the anti-HIB antibody production in groups vaccinated with Act-HIB. +. ViscoGel. ELISpot analyses revealed increased interferon-γ (IFN-γ) responses to Act-HIB in PBMCs from subjects vaccinated with Act-HIB in combination with ViscoGel, compared to groups receiving Act-HIB alone. Moreover, ViscoGel counteracted an inhibitory effect of Act-HIB vaccination on the IFN-γ response to both the vaccine itself and an irrelevant influenza antigen. In summary, ViscoGel was found to be safe and well-tolerated, supporting further examination of ViscoGel as a new innovative vehicle for vaccine development. © 2014 Elsevier Ltd. Source


Franzen H.M.,Viscogel AB | Draget K.I.,Norwegian University of Science and Technology | Langeback J.,Viscogel AB | Nilsen-Nygaard J.,Norwegian University of Science and Technology
Polymers | Year: 2015

The current paper focuses on the preparation and some characteristics of viscoelastic hydrogels, ViscoGels™, made from chitosans having a random acylation pattern. Three different chitosan batches with a high fraction of acetylation were selected based on their Mw, and the impact of degree of cross-linking on these chitosan samples has been studied with respect to the properties of the final hydrogels. Rheological long term (12 month) stability and gelling kinetics data are presented together with results from swelling studies at different pH. Finally, an example illustrating these gels potential as drug delivery vehicles is presented and discussed. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source


Neimert-Andersson T.,Karolinska Institutet | Neimert-Andersson T.,Viscogel AB | Hallgren A.-C.,Viscogel AB | Andersson M.,Viscogel AB | And 9 more authors.
Vaccine | Year: 2011

An immune response to an antigen is more efficiently induced in combination with an adjuvant. Chitosan has due to documented immunostimulatory characteristics been proposed as an adjuvant candidate. However, a disadvantage with chitosan is its poor solubility at physiological pH. We have circumvented this obstacle by using a soluble type of chitosan (Viscosan), with a degree of deacetylation (DD) of 50% and a random distribution of acetyl groups. A hydrogel, ViscoGel, was made from Viscosan which was further mechanically processed into gel particles of predefined size. The first cells to infiltrate ViscoGel in mice, were identified mainly as neutrophils, detected already after 4. h. ViscoGel's impact on the immune response in mice together with a commercial vaccine against Haemophilus influenzae type b (Act-HIB) was then studied. Mixing Act-HIB with ViscoGel, induced significantly enhanced IgG1 and IgG2a titers in serum (p< 0.05). We could reduce the antigen dose ten-fold in combination with ViscoGel and still obtain antibody titers similar to 2 μg Act-HIB administered alone. In addition, the Act-HIB specific cellular response was stronger in mice vaccinated together with ViscoGel (p< 0.05). The cytokine response after vaccination with Act-Hib together with ViscoGel was of a mixed type. We found elevated levels of the Th1 associated cytokine INF-γ, the Th2-cytokine IL-4, the proinflammatory IL-6 and IL-17A, and the regulatory cytokine IL-10. Similar effects were seen when the adjuvant was administered either subcutaneously or intramuscularly. Taken together, using vaccination against H. influenzae type b as a model, we here show proof of concept for the novel vaccine adjuvant candidate, ViscoGel. © 2011 Elsevier Ltd. Source

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