| 1. |
- Akgün, J., et al.
(författare)
-
The role of alveolar epithelial type II-Like cells in uptake of structurally different antigens and in polarisation of local immune responses
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background Our previous studies on intranasal tolerance induction demonstrated reduction of allergic responses with different allergen constructs. The underlying mechanisms varied depending on their conformation or size. Objective The aim of the present study was to compare the uptake of two structurally different allergen molecules within the respiratory tract following intranasal application. Methods The three-dimensional Bet v 1 (Bv1-Protein) and the T cell epitope peptide of Bet v 1 (Bv1- Peptide) were labelled with 5,6-Carboxyfluorescein (FAM) and their uptake was investigated in lung cells and cells of the nasal associated lymphoid tissue from naive and sensitised BALB/c mice. Phenotypic characterisation of FAM+ lung cells after antigen incubation in vitro and after intranasal application was performed by flow cytometry. Impact of Bv1-Protein and Bv1-Peptide on cytokine profiles and gene expression in vivo or in an alveolar epithelial type II (ATII) cell line were assessed in mono- and co-cultures with monocytes using ELISA and quantitative real-time PCR. Results Both antigens were taken up preferably by ATII-like cells (ATII-LCs) in naive mice, and by macrophages in sensitised mice. After intranasal application, Bv1-Peptide was taken up faster and more efficiently than Bv1-Protein. In vivo and in vitro experiments revealed that Bv1-Protein induced the transcription of thymic stromal lymphopoietin mRNA while Bv1- Peptide induced the transcription of IL-10 and MCP1 mRNA in ATII-LCs. Conclusion and Clinical Relevance Both tested antigens were taken up by ATII-LCs under steady state conditions and induced different polarisation of the immune responses. These data may have an important impact for the generation of novel and more effective prophylactic or therapeutic tools targeting the respiratory mucosa. Copyright: © 2015 Akgün et al.
|
|
| 2. |
- Gattinger, Pia, et al.
(författare)
-
Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants
- 2022
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:8, s. 2431-2445
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global COVID-19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS-CoV-2 from entering human cells to replicate in.Methods: We report the construction and in vitro and in vivo characterization of a SARS-CoV-2 subunit vaccine (PreS-RBD) based on a structurally folded recombinant fusion protein consisting of two SARS-CoV-2 Spike protein receptor-binding domains (RBD) fused to the N- and C-terminus of hepatitis B virus (HBV) surface antigen PreS to enable the two unrelated proteins serving as immunologic carriers for each other.Results: PreS-RBD, but not RBD alone, induced a robust and uniform RBD-specific IgG response in rabbits. Currently available genetic SARS-CoV-2 vaccines induce mainly transient IgG1 responses in vaccinated subjects whereas the PreS-RBD vaccine induced RBD-specific IgG antibodies consisting of an early IgG1 and sustained IgG4 antibody response in a SARS-CoV-2 naive subject. PreS-RBD-specific IgG antibodies were detected in serum and mucosal secretions, reacted with SARS-CoV-2 variants, including the omicron variant of concern and the HBV receptor-binding sites on PreS of currently known HBV genotypes. PreS-RBD-specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus-neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS-CoV-2 vaccines or in COVID-19 convalescent subjects.Conclusion: The PreS-RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS-CoV-2 and HBV by stopping viral replication through the inhibition of cellular virus entry.
|
|
| 3. |
- Wagner, A., et al.
(författare)
-
Paediatricians require more information before they routinely co-administer the meningococcal B vaccine with routine infant vaccines
- 2015
-
Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253. ; 104:10
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: The four-component meningococcal serogroup B (4CMenB) vaccine was licensed by the European Medicines Agency in 2013. We evaluated current practice regarding multiple vaccines and the attitudes of paediatricians towards the 4CMenB before it became available in Austria in 2014. Methods: We sent 1624 Austrian paediatricians an email invitation to participate in our nationwide web-based survey and 231 responded. Results: Most participants regarded the 4CMenB vaccine as a long-needed and necessary tool against meningococcal B disease. However, most participants would not co-administer this vaccine with other routine infant vaccines. The survey showed that 58.9% of paediatricians already co-administered the hexavalent vaccine with the pneumococcal conjugate vaccine, but most of them would not add a third vaccine at the same visit. This was mainly due to lack of experience with the vaccine and also because they assumed that parents would not consent. Importantly, paediatricians said they wanted an explicit recommendation in the Austrian Immunisation Plan on the timing of the 4CMenB vaccine before they would confidently and routinely use it for infants. Conclusion: Paediatricians required more information for themselves and for parents before routinely co-administering the 4CMenB vaccine. They also requested a national recommendation on its timing.
|
|
| 4. |
- Wagner, A., et al.
(författare)
-
Prime-Boost Vaccination with Toxoplasma Lysate Antigen, but Not with a Mixture of Recombinant Protein Antigens, Leads to Reduction of Brain Cyst Formation in BALB/c Mice
- 2015
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Infection with the ubiquitous parasite Toxoplasma gondii is a threat for immunocompromised patients and pregnant women and effective immune-prophylaxis is still lacking. Here we tested a mixture of recombinant T. gondii antigens expressed in different developmental stages, i.e., SAG1, MAG1 and GRA7 (SMG), and a lysate derived from T. gondii tachyzoites (TLA) for prophylactic vaccination against cyst formation. Both vaccine formulations were applied systemically followed by an oral TLA-booster in BALB/c mice. Systemic priming with SMG and oral TLA-booster did not show significant induction of protective immune responses. In contrast, systemic priming and oral booster with TLA induced higher levels of Toxoplasma-specific IgG, IgG1 and IgG2a in sera as well as high levels of Toxoplasma-specific IgG1 in small intestines. Furthermore, high levels of Toxoplasma-specific Th1-, Th17-and Th2-associated cytokines were only detected in restimulated splenocytes of TLA-vaccinated mice. Importantly, in mice orally infected with T. gondii oocysts, only TLA-vaccination and booster reduced brain cysts. Furthermore, sera from these mice reduced tachyzoites invasion of Vero cells in vitro, indicating that antibodies may play a critical role for protection against Toxoplasma infection. Additionally, supernatants from splenocyte cultures of TLA-vaccinated mice containing high levels of IFN-gamma lead to substantial production of nitric oxide (NO) after incubation with macrophages in vitro. Since NO is involved in the control of parasite growth, the high levels of IFN-gamma induced by vaccination with TLA may contribute to the protection against T. gondii. In conclusion, our data indicate that prime-boost approach with TLA, but not with the mixture of recombinant antigens SMG, induces effective humoral and cellular Toxoplasma-specific responses and leads to significant reduction of cerebral cysts, thereby presenting a viable strategy for further vaccine development against T. gondii infection.
|
|
