Publications by authors named "Ursula Wiedermann"

94 Publications

Reduction of Allergic Lung Disease by Mucosal Application of -Derived Molecules: Possible Role of Carbohydrates.

Front Immunol 2020 10;11:612766. Epub 2021 Mar 10.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

Background: The hygiene hypothesis suggests a link between parasitic infections and immune disorders, such as allergic diseases. We previously showed that infection with or systemic application of tachyzoites lysate antigen (TLA) in a prophylactic, but not therapeutic protocol, prevented allergic airway inflammation in mice. Here we tested the effect of prophylactic and therapeutic application of TLA the mucosal route.

Methods: Mice were intranasally treated with TLA either i) prior to sensitization, ii) during sensitization and challenge, or iii) after sensitization with ovalbumin (OVA). Recruitment of inflammatory cells to the lung, cytokine levels in restimulated lung and spleen cell cultures as well as levels of OVA-specific antibodies in serum were measured. In parallel, the effect of native TLA, heat-inactivated (hiTLA) or deglycosylated TLA (dgTLA) on sensitized splenocytes was evaluated .

Results: When applied together with OVA i) during systemic sensitization and local challenge or ii) exclusively during local challenge, TLA reduced infiltration of eosinophils into the lung, OVA-specific type 2 cytokines in restimulated lung cell cultures, and partially, type 2 cytokines in restimulated spleen cell cultures in comparison to allergic controls. No beneficial effect was observed when TLA was applied prior to the start of sensitization. Analysis of epitope sugars on TLA indicated a high abundance of mannose, fucose, N-acetylglucosamine, and N-acetylgalactosamine. Deglycosylation of TLA, but not heat-inactivation, abolished the potential of TLA to reduce type 2 responses , suggesting a significant role of carbohydrates in immunomodulation.

Conclusion: We showed that mucosal application of TLA reduced the development of experimental allergy in mice. The beneficial effects depended on the timing of the application in relation to the time point of sensitization. Not only co-application, but also therapy in sensitized/allergic animals with native TLA reduced local allergic responses. Furthermore, we show that TLA is highly glycosylated and glycoconjugates seem to play a role in anti-allergic effects. In summary, given the powerful modulatory effect that TLA exhibits, understanding its exact mechanisms of action may lead to the development of novel immunomodulators in clinical application.
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http://dx.doi.org/10.3389/fimmu.2020.612766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988086PMC
March 2021

Pre- and Neonatal Imprinting on Immunological Homeostasis and Epithelial Barrier Integrity by Nissle 1917 Prevents Allergic Poly-Sensitization in Mice.

Front Immunol 2020 17;11:612775. Epub 2021 Feb 17.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

A steady rise in the number of poly-sensitized patients has increased the demand for effective prophylactic strategies against multi-sensitivities. Probiotic bacteria have been successfully used in clinics and experimental models to prevent allergic mono-sensitization. In the present study, we have investigated whether probiotic bacteria could prevent poly-sensitization by imprinting on the immune system early in life. We used two recombinant variants of probiotic Nissle 1917 (EcN): i) EcN expressing birch and grass pollen, poly-allergen chimera construct (EcN-Chim), and ii) an "empty" EcN without allergen expression (EcN-Ctrl). Conventional mice (CV) were treated with either EcN-Chim or EcN-Ctrl in the last week of the gestation and lactation period. Gnotobiotic mice received one oral dose of either EcN-Chim or EcN-Ctrl before mating. The offspring from both models underwent systemic allergic poly-sensitization and intranasal challenge with recombinant birch and grass pollen allergens (rBet v 1, rPhl p 1, and rPhl p 5). In the CV setting, the colonization of offspring treatment of mothers reduced allergic airway inflammation (AAI) in offspring compared to poly-sensitized controls. Similarly, in a gnotobiotic model, AAI was reduced in EcN-Chim and EcN-Ctrl mono-colonized offspring. However, allergy prevention was more pronounced in the EcN-Ctrl mono-colonized offspring as compared to EcN-Chim. Mono-colonization with EcN-Ctrl was associated with a shift toward mixed Th1/Treg immune responses, increased expression of TLR2 and TLR4 in the lung, and maintained levels of zonulin-1 in lung epithelial cells as compared to GF poly-sensitized and EcN-Chim mono-colonized mice. This study is the first one to establish the model of allergic poly-sensitization in gnotobiotic mice. Using two different settings, gnotobiotic and conventional mice, we demonstrated that an early life intervention with the EcN without expressing an allergen is a powerful strategy to prevent poly-sensitization later in life.
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http://dx.doi.org/10.3389/fimmu.2020.612775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927790PMC
February 2021

Isolate-Based Surveillance of Bordetella pertussis, Austria, 2018-2020.

Emerg Infect Dis 2021 Mar;27(3):862-871

Pertussis is a vaccine-preventable disease, and its recent resurgence might be attributable to the emergence of strains that differ genetically from the vaccine strain. We describe a novel pertussis isolate-based surveillance system and a core genome multilocus sequence typing scheme to assess Bordetella pertussis genetic variability and investigate the increased incidence of pertussis in Austria. During 2018-2020, we obtained 123 B. pertussis isolates and typed them with the new scheme (2,983 targets and preliminary cluster threshold of <6 alleles). B. pertussis isolates in Austria differed genetically from the vaccine strain, both in their core genomes and in their vaccine antigen genes; 31.7% of the isolates were pertactin-deficient. We detected 8 clusters, 1 of them with pertactin-deficient isolates and possibly part of a local outbreak. National expansion of the isolate-based surveillance system is needed to implement pertussis-control strategies.
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http://dx.doi.org/10.3201/eid2703.202314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920692PMC
March 2021

Editorial: Challenges in Vaccinology.

Front Immunol 2020 17;11:632537. Epub 2020 Dec 17.

Institute of Specific Prophylaxis and Tropical Medicine, Center of Pathophysiology, Infectiology & Immunology, Medical University Vienna, Vienna, Austria.

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http://dx.doi.org/10.3389/fimmu.2020.632537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773695PMC
December 2020

Towards understanding vaccine hesitancy and vaccination refusal in Austria.

Wien Klin Wochenschr 2020 Dec 11. Epub 2020 Dec 11.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

In Austria, data on vaccine hesitancy is scarce. Available studies suggest around 1-11% of parents refuse vaccination, while many more are hesitant and consider refraining from some but not all of the recommended vaccinations. However, the key drivers for vaccine hesitancy in Austria are largely unknown. To learn more about vaccination coverage, attitude towards and knowledge around immunization as well as views on mandatory vaccination, we conducted a survey in a rural Austrian lay population including adults and children. Two paper-based questionnaires, one for adults 16 years or older and one for children aged 6-15 years, were developed, then sent to all houses of a rural community in Austria as well as handed out at the local primary and middle school, respectively. Self-reported coverage rates of children and adults were found to be low. Within the surveyed population 3% of children had never been or do not get vaccinated. More than half (57%) of the survey participants had a positive attitude towards vaccines, 21% were without reserves, 16% were found skeptical and 5% had a generally negative attitude. Knowledge about immunization in general was poor. Younger adults and people with secondary education appear to be most skeptical and negative towards vaccination. Children's attitudes were closely linked to those of their parents. The major concern around vaccination in adults was fear of side effects. In adults, 54.2% support mandatory vaccination for Health Care Workers and 20.7% are against it. 39% of adults and 37% of children wanted more information on vaccination, preferably provided by physicians. Knowledge about disease prevention by vaccination should be improved and children could also benefit from an early age-appropriate vaccine education to strengthen health literacy. Physicians are the most trusted source of health information. Medical doctors should be aware of their very important role in transmitting trusted health information. This should include an up-to-date education in communicable disease prevention and immunization during their whole medical career. Furthermore, the curricula of health-care workers may need to be improved and harmonized concerning prevention and vaccination.
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http://dx.doi.org/10.1007/s00508-020-01777-9DOI Listing
December 2020

Cross-Reactive Effects of Vaccines: Heterologous Immunity between Tetanus and Chlamydia.

Vaccines (Basel) 2020 Dec 1;8(4). Epub 2020 Dec 1.

Center for Pathophysiology Infectiology and Immunology, Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, 1090 Vienna, Austria.

Vaccines can have heterologous effects on the immune system, i.e., effects other than triggering an immune response against the disease targeted by the vaccine. We investigated whether monoclonal antibodies (mAbs) specific for tetanus could cross-react with Chlamydia and confer heterologous protection against chlamydial infection. The capability of two tetanus-specific mAbs, namely mAb26 and mAb51, to prevent chlamydial infection has been assessed: (i) in vitro, by performing a neutralization assay using human conjunctival epithelial (HCjE) cells infected with serovar B, and (ii) in vivo, by using a guinea pig model of -induced inclusion conjunctivitis. The mAb26 has been superior in comparison with mAb51 in the prevention of chlamydial infection in HCjE cells. The mAb26 has conferred ≈40% inhibition of the infection, compared to less than 5% inhibition in the presence of the mAb51. In vivo, mAb26 significantly diminished ocular pathology intensity in guinea pigs infected with compared to either the mAb51-treated or sham-treated guinea pigs. Our data provide insights that tetanus immunization generates antibodies which induce heterologous chlamydial immunity and promote protection beyond the intended target pathogen.
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http://dx.doi.org/10.3390/vaccines8040719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712554PMC
December 2020

Machine Learning-Empowered FTIR Spectroscopy Serum Analysis Stratifies Healthy, Allergic, and SIT-Treated Mice and Humans.

Biomolecules 2020 07 16;10(7). Epub 2020 Jul 16.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, 1090 Vienna, Austria.

The unabated global increase of allergic patients leads to an unmet need for rapid and inexpensive tools for the diagnosis of allergies and for monitoring the outcome of allergen-specific immunotherapy (SIT). In this proof-of-concept study, we investigated the potential of Fourier-Transform Infrared (FTIR) spectroscopy, a high-resolution and cost-efficient biophotonic method with high throughput capacities, to detect characteristic alterations in serum samples of healthy, allergic, and SIT-treated mice and humans. To this end, we used experimental models of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific tolerance induction in BALB/c mice. Serum collected before and at the end of the experiment was subjected to FTIR spectroscopy. As shown by our study, FTIR spectroscopy, combined with deep learning, can discriminate serum from healthy, allergic, and tolerized mice, which correlated with immunological data. Furthermore, to test the suitability of this biophotonic method for clinical diagnostics, serum samples from human patients were analyzed by FTIR spectroscopy. In line with the results from the mouse models, machine learning-assisted FTIR spectroscopy allowed to discriminate sera obtained from healthy, allergic, and SIT-treated humans, thereby demonstrating its potential for rapid diagnosis of allergy and clinical therapeutic monitoring of allergic patients.
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http://dx.doi.org/10.3390/biom10071058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408032PMC
July 2020

A New Strategy Toward B Cell-Based Cancer Vaccines by Active Immunization With Mimotopes of Immune Checkpoint Inhibitors.

Front Immunol 2020 27;11:895. Epub 2020 May 27.

Center for Pathophysiology, Infectiology and Immunology, Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warrant further development and modification to gain more flexibility for this immunotherapy approach. An attractive alternative to passive immunization with therapeutic antibodies might be active immunization with mimotopes (B-cell peptides) representing the mAbs' binding epitopes, to activate the patient's own anti-tumor immune response following immunization. Here, we identified and examined the feasibility of inducing anti-tumor effects following active immunization with a mimotope of the immune checkpoint programmed cell death 1 (PD1), alone or in combination with a Her-2/neu B-cell peptide vaccine. Overlapping peptides spanning the extracellular domains of human PD1 (hPD1) were used to identify hPD1-derived mimotopes, using the therapeutic mAb Nivolumab as a proof of concept. Additionally, for evaluation in a tumor mouse model, a mouse PD1 (mPD1)-derived mimotope was identified using an anti-mPD1 mAb with mPD1/mPDL-1 blocking capacity. The identified mimotopes were characterized by assays, including a reporter cell-based assay, and their anti-tumor effects were evaluated in a syngeneic tumor mouse model stably expressing human Her-2/neu. The identified PD1-derived mimotopes were shown to significantly block the mAbs' capacity in inhibiting the respective PD1/PD-L1 interactions. A significant reduction in tumor growth was observed following active immunization with the mPD1-derived mimotope, associated with a significant reduction in proliferation and increased apoptotic rates in the tumors. Particularly, combined vaccination with the mPD1-derived mimotope and a multiple B-cell epitope Her-2/neu vaccine potentiated the vaccine's anti-tumor effect. Our results suggest active immunization with mimotopes of immune checkpoint inhibitors either as monotherapy or as combination therapy with tumor-specific vaccines, as a new strategy for cancer treatment.
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http://dx.doi.org/10.3389/fimmu.2020.00895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266955PMC
April 2021

Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination.

Front Immunol 2020 27;11:860. Epub 2020 May 27.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

Obesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction and increased susceptibility to infections. Thus, prophylaxis against vaccine-preventable diseases is crucial, yet the responsiveness to several vaccines is unclear under obesity. In order to assess the responsiveness to tick-borne encephalitis (TBE) vaccine, we revaccinated 37 obese individuals and 36 normal-weight controls with a licensed TBE vaccine. Metabolic, hormonal, and immunologic profiles along with vaccine-specific humoral and cellular immune responses were evaluated in sera and peripheral blood mononuclear cells (PBMCs) before, 1 week, 4 weeks, and 6 months after TBE booster. Obese adults had significantly increased metabolic (triglycerides, cholesterol ratios, leptin, insulin) and proinflammatory (C-reactive protein) parameters. They showed stronger initial increase of TBE-specific Ab titers (d7_d28) followed by a significantly faster decline after 6 months, which correlated with high body mass index and leptin and insulin levels. The fold increase of Ab-titer levels was significantly higher in obese compared to control males and linked to reduced testosterone levels. Obesity also affected cellular responses: PBMCs of the obese vaccinees had elevated interleukin 2 and interferon γ levels upon antigen stimulation, indicating a leptin-dependent proinflammatory T1 polarization. The expansion of total and naive B cells in obese might explain the initial increase of Ab titers, whereas the reduced B-memory cell and plasma blast generation could be related to fast Ab decline with a limited maintenance of titers. Among T follicular helper cell (Tfh) cells, the Tfh17 subset was significantly expanded particularly in obese males, where we observed a strong initial Ab increase. Systemic but not local vaccine side effects were more frequent in obese subjects as a possible consequence of their low-grade proinflammatory state. In summary, TBE booster vaccination was effective in obese individuals, yet the faster Ab decline could result in a reduced long-term protection. The sex-based differences in vaccine responses indicate a complex interplay of the endocrine, metabolic, and immune system during obesity. Further studies on the long-term protection after vaccination are ongoing, and also evaluation of primary vaccination against TBE in obese individuals is planned. NCT04017052; https://clinicaltrials.gov/ct2/show/NCT04017052.
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http://dx.doi.org/10.3389/fimmu.2020.00860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266951PMC
April 2021

A novel 5-Plex qPCR-HRM assay detecting human diarrheal parasites.

Gut Pathog 2020 29;12:27. Epub 2020 May 29.

Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria.

Background: Intestinal parasitic diseases occur worldwide, and their diagnosis poses considerable challenges. spp., (and, arguably, and spp.) are among the most important and common parasitic protozoans causing diarrhea. Several multiplex real-time PCR assays have been developed for the synchronous detection of these parasites. However, most assays include the use of hydrolysis probes, increasing the cost of stool examination. In this study, we designed and evaluated a real-time PCR protocol, based on high-resolution melting (HRM) curve analysis, to simultaneously detect and differentiate five gastrointestinal parasites.

Results: Using a blinded panel of 143 clinical samples with laboratory diagnostic data to evaluate the method, we obtained a 95.8% concordance with conventional methods. Moreover, 4.2% of the samples were positive for and 2.8% additional infections were found with our multiplex assay. Our method is sensitive and specific for the selected parasites with the additional possibility of being run in single-plex as a backup control for mixed infections.

Conclusions: The assay is a convenient and cost-effective method that could contribute to a quicker and accurate diagnosis as well as to more targeted therapies of parasite-derived diarrhea. Finally, this new multiplex PCR assay could also be instrumental in epidemiology studies on these parasites.
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http://dx.doi.org/10.1186/s13099-020-00365-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257150PMC
May 2020

Vaccination of healthcare personnel in Europe: Update to current policies.

Vaccine 2019 12 14;37(52):7576-7584. Epub 2019 Oct 14.

Director, Mayo Vaccine Research Group, Mayo Clinic, Rochester, MN, United States.

We investigated and compared current national vaccination policies for health-care personnel (HCP) in Europe with results from our previous survey. Data from 36 European countries were collected using the same methodology as in 2011. National policies for HCP immunization were in place in all countries. There were significant differences in terms of number of vaccinations, target HCP and healthcare settings, and implementation regulations (recommended or mandatory vaccinations). Vaccination policies against hepatitis B and seasonal influenza were present in 35 countries each. Policies for vaccination of HCP against measles, mumps, rubella and varicella existed in 28, 24, 25 and 19 countries, respectively; and against tetanus, diphtheria, pertussis and poliomyelitis in 21, 20, 19, and 18 countries, respectively. Recommendations for hepatitis A immunization existed in 17 countries, and against meningococcus B, meningococcus C, meningococcus A, C, W, Y, and tuberculosis in 10, 8, 17, and 7 countries, respectively. Mandatory vaccination policies were found in 13 countries and were a pre-requisite for employment in ten. Comparing the vaccination programs of the 30 European countries that participated in the 2011 survey, we found that more countries had national vaccination policies against measles, mumps, rubella, hepatitis A, diphtheria, tetanus, poliomyelitis, pertussis, meningococcus C and/or meningococcus A, C, W, Y; and more of these implemented mandatory vaccination policies for HCP. In conclusion, European countries now have more comprehensive national vaccination programs for HCP, however there are still gaps. Given the recent large outbreaks of vaccine-preventable diseases in Europe and the occupational risk for HCP, vaccination policies need to be expanded and strengthened in several European countries. Overall, vaccination policies for HCP in Europe should be periodically re-evaluated in order to provide optimal protection against vaccine-preventable diseases and infection control within healthcare facilities for HCP and patients.
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http://dx.doi.org/10.1016/j.vaccine.2019.09.061DOI Listing
December 2019

Therapeutic PD-L1 antibodies are more effective than PD-1 antibodies in blocking PD-1/PD-L1 signaling.

Sci Rep 2019 08 7;9(1):11472. Epub 2019 Aug 7.

Division of Immune Receptors and T Cell Activation, Center for Pathophysiology, Infectiology, Medical University of Vienna, Vienna, Austria.

Inhibitors of PD-1 signaling have revolutionized cancer therapy. PD-1 and PD-L1 antibodies have been approved for the treatment of cancer. To date, therapeutic PD-1 inhibitors have not been compared in a functional assay. We used an efficient T cell reporter platform to evaluate the efficacy of five clinically used PD-1 inhibitors to block PD-1 signaling. The half maximal effective concentrations (EC) for nivolumab and pembrolizumab were 76.17 ng/ml (95% CI 64.95-89.34 ng/ml) and 39.90 ng/ml (34.01-46.80 ng/ml), respectively. The EC values of the PD-L1 inhibitors were 6.46 ng/ml (5.48-7.61 ng/ml), 6.15 ng/ml (5.24-7.21 ng/ml) and 7.64 ng/ml (6.52-8.96 ng/ml) for atezolizumab, avelumab, and durvalumab, respectively. In conclusion, a functional assay evaluating antibodies targeting PD-1 inhibition in vitro revealed that pembrolizumab is a slightly more effective PD-1 blocker than nivolumab, and that PD-L1 antibodies are superior to PD-1 antibodies in reverting PD-1 signaling.
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http://dx.doi.org/10.1038/s41598-019-47910-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685986PMC
August 2019

Mandatory vaccination: suited to enhance vaccination coverage in Europe?

Euro Surveill 2019 Jun;24(26)

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria.

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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.26.1900376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607742PMC
June 2019

The zinc-finger transcription factor MAZR regulates iNKT cell subset differentiation.

Cell Mol Life Sci 2019 Nov 7;76(21):4391-4404. Epub 2019 May 7.

Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria.

Invariant natural killer T (iNKT) cells represent a subgroup of innate-like T cells and play an important role in immune responses against certain pathogens. In addition, they have been linked to autoimmunity and antitumor immunity. iNKT cells consist of several subsets with distinct functions; however, the transcriptional networks controlling iNKT subset differentiation are still not fully characterized. Myc-associated zinc-finger-related factor (MAZR, also known as PATZ1) is an essential transcription factor for CD8 lineage differentiation of conventional T cells. Here, we show that MAZR plays an important role in iNKT cells. T-cell lineage-specific deletion of MAZR resulted in an iNKT cell-intrinsic defect that led to an increase in iNKT2 cell numbers, concurrent with a reduction in iNKT1 and iNKT17 cells. Consistent with the alteration in the subset distribution, deletion of MAZR also resulted in an increase in the percentage of IL-4-producing cells. Moreover, MAZR-deficient iNKT cells displayed an enhanced expression of Erg2 and ThPOK, key factors for iNKT cell generation and subset differentiation, indicating that MAZR controls iNKT cell development through fine-tuning of their expression levels. Taken together, our study identified MAZR as an essential transcription factor regulating iNKT cell subset differentiation and effector function.
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http://dx.doi.org/10.1007/s00018-019-03119-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803753PMC
November 2019

Germ-Free Mice Exhibit Mast Cells With Impaired Functionality and Gut Homing and Do Not Develop Food Allergy.

Front Immunol 2019 12;10:205. Epub 2019 Feb 12.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

Mucosal mast cells (MC) are key players in IgE-mediated food allergy (FA). The evidence on the interaction between gut microbiota, MC and susceptibility to FA is contradictory. We tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA. The development and severity of FA symptoms was studied in sensitized germ-free (GF), conventional (CV), and mice mono-colonized with WCFS1 or co-housed with CV mice. MC were phenotypically and functionally characterized. Systemic sensitization and oral challenge of GF mice with ovalbumin led to increased levels of specific IgE in serum compared to CV mice. Remarkably, despite the high levels of sensitization, GF mice did not develop diarrhea or anaphylactic hypothermia, common symptoms of FA. In the gut, GF mice expressed low levels of the MC tissue-homing markers CXCL1 and CXCL2, and harbored fewer MC which exhibited lower levels of MC protease-1 after challenge. Additionally, MC in GF mice were less mature as confirmed by flow-cytometry and their functionality was impaired as shown by reduced edema formation after injection of degranulation-provoking compound 48/80. Co-housing of GF mice with CV mice fully restored their susceptibility to develop FA. However, this did not occur when mice were mono-colonized with . Our results demonstrate that microbiota-induced maturation and gut-homing of MC is a critical step for the development of symptoms of experimental FA. This new mechanistic insight into microbiota-MC-FA axis can be exploited in the prevention and treatment of FA in humans.
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http://dx.doi.org/10.3389/fimmu.2019.00205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379318PMC
January 2020

Invasive pneumococcal diseases in children and adults before and after introduction of the 10-valent pneumococcal conjugate vaccine into the Austrian national immunization program.

PLoS One 2019 10;14(1):e0210081. Epub 2019 Jan 10.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

Background: In February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study.

Methods: The study period was divided into pre- (2009-2011) and post-period (2013-2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5-49 and ≥50 years old. Additionally, for the 5-49 and ≥50 years old, and the 50-59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression.

Results: The PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5-49 years old.

Conclusions: Our study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210081PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328268PMC
September 2019

Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial.

Lancet 2019 12 5;392(10165):2718-2727. Epub 2018 Nov 5.

Themis, Vienna, Austria.

Background: Chikungunya fever is an emerging viral disease and substantial threat to public health. We aimed to assess the safety, tolerability, and immunogenicity of a live-attenuated, measles-vectored chikungunya vaccine (MV-CHIK).

Methods: In this double-blind, randomised, placebo-controlled and active-controlled phase 2 trial, we enrolled healthy volunteers aged 18-55 years at four study sites in Austria and Germany. Participants were randomly assigned to receive intramuscular injections with MV-CHIK (5 × 10 or 5 × 10 50% tissue culture infectious dose), control vaccine, or measles prime and MV-CHIK, in two different administration regimens. Randomisation was done by use of three-digit randomisation codes in envelopes provided by a data management service. The participants and investigators were masked to treatment assignment, which was maintained by use of sterile saline as a placebo injection. The primary endpoint was immunogenicity, defined as the presence of neutralising antibodies against chikungunya virus, at day 56, which is 28 days after one or two immunisations. The primary endpoint was assessed in all participants who completed the study without major protocol deviations (per-protocol population) and in all randomised participants who received at least one study treatment (modified intention-to-treat population). The safety analysis included all participants who received at least one study treatment. This trial is registered with ClinicalTrials.gov (NCT02861586) and EudraCT (2015-004037-26) and is completed.

Findings: Between Aug 17, 2016, and May 31, 2017, we randomly assigned 263 participants to receive control vaccine (n=34), MV-CHIK (n=195), or measles prime and MV-CHIK (n=34). 247 participants were included in the per-protocol population. Neutralising antibodies against chikungunya virus were detected in all MV-CHIK treatment groups after one or two immunisations, with geometric mean titres ranging from 12·87 (95% CI 8·75-18·93) to 174·80 (119·10-256·50) and seroconversion rates ranging from 50·0% to 95·9% depending on the dose and administration schedule. Adverse events were similar between groups, with solicited adverse events reported in 168 (73%) of 229 participants assigned to MV-CHIK and 24 (71%) of 34 assigned to control vaccine (p=0·84) and unsolicited adverse events in 116 (51%) participants assigned to MV-CHIK and 17 (50%) assigned to control vaccine (p=1·00). No serious adverse events related to the vaccine were reported.

Interpretation: MV-CHIK showed excellent safety and tolerability and good immunogenicity, independent of pre-existing immunity against the vector. MV-CHIK is a promising candidate vaccine for the prevention of chikungunya fever, an emerging disease of global concern.

Funding: Themis.
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http://dx.doi.org/10.1016/S0140-6736(18)32488-7DOI Listing
December 2019

Prophylactic and therapeutic inhibition of allergic airway inflammation by probiotic Escherichia coli O83.

J Allergy Clin Immunol 2018 12 17;142(6):1987-1990.e7. Epub 2018 Aug 17.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.07.029DOI Listing
December 2018

Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules.

Sci Rep 2018 06 29;8(1):9825. Epub 2018 Jun 29.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, 1090, Austria.

Immunosenescence is characterised by reduced B and T cell responses. Evidence shows that booster vaccinations are less effective in elderly people, but data on the efficacy of primary immunisation are sparse. We conducted a monocentric, open label, phase IV trial to compare immune responses to primary vaccinations using the inactivated, adjuvanted Japanese Encephalitis vaccine by 30 elderly people (mean 69, range 61-78 years) and 30 younger people (mean 24, range 18-30 years). Humoral and cellular immune responses were analysed in relation to age and cytomegalovirus (CMV) seropositivity. Vaccine-specific antibody titres were significantly lower in elderly participants and 47% of them were non- or low responders after the two doses of the vaccine neo-antigen. The reduced humoral immune responses in elderly people correlated with reduced cytokine production, such as interferon gamma (IFN-γ) in vitro, as well as higher frequencies of late-differentiated effector and effector memory T cells and T regulatory cells. These cellular changes and lower antibody titres were particularly prominent in CMV-seropositive elderly participants. If primary vaccination before the age of 60 is not possible, elderly patients may require different vaccination strategies to ensure sufficient long-lasting immunity, such as adapted or accelerated schedules and the use of different adjuvants.
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http://dx.doi.org/10.1038/s41598-018-28111-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026142PMC
June 2018

Allergic patients with and without allergen-specific immunotherapy mount protective immune responses to tick-borne encephalitis vaccination in absence of enhanced side effects or propagation of their Th2 bias.

Vaccine 2018 05 16;36(20):2816-2824. Epub 2018 Apr 16.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna Kinderspitalgasse 15, A-1090 Vienna, Austria. Electronic address:

Background: Allergic diseases are caused by Th2-driven immune responses and their treatment with specific immunotherapy (SIT) leads to immunomodulation via IL10, TGF-ß and Th1/Tr1 shift. This phase IV, open-label clinical trial investigated whether allergies and SIT treatment influenced immune responses to routine vaccination.

Methods: We studied three groups: 49 allergic patients (allergic group), 21 allergic patients receiving maintenance doses of SIT (SIT group), and 49 non-allergic controls. All subjects received tick-borne encephalitis (TBE) booster vaccines and humoral and cellular immune responses were evaluated after one week, four weeks and six months.

Results: The levels and kinetics of neutralizing TBE-specific antibodies, reflecting protection against TBE, were not significantly different in the three groups. The allergic group showed Th2 polarization pre-booster as indicated by increased TBE-specific IgG1 and elevated mitogen-induced IL5 production. Alum-adjuvanted TBE vaccine led to Th2 biased immune responses in the controls, but to no further enhancement of Th2 polarization in the allergic and SIT group. Furthermore, in the SIT group cellular parameters reflected the induction of immunomodulation due to increased Tregs, elevated baseline IL10 and lack of TBE-specific IL5. Importantly, these cellular regulatory responses did not limit the ability to mount sufficient TBE-specific antibodies after the booster. All groups tolerated the vaccine well with no exacerbation of allergic symptoms.

Conclusion: TBE booster vaccinations were immunogenic and safe in both the allergic and SIT group and contributed to balanced immune responses. Our data indicate that all allergic patients, even when undergoing SIT, should be vaccinated without hesitation and at regular intervals according to standard recommendations. ClinicalTrials.gov (NCT02511535).
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http://dx.doi.org/10.1016/j.vaccine.2018.03.076DOI Listing
May 2018

Toxoplasma gondii tachyzoite-extract acts as a potent immunomodulator against allergic sensitization and airway inflammation.

Sci Rep 2017 11 9;7(1):15211. Epub 2017 Nov 9.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

Epidemiological and experimental studies have shown an inverse relationship between infections with certain parasites and a reduced incidence of allergic diseases. We and others have shown that infection with Toxoplasma gondii prevents the development of allergy in mice. To establish whether this beneficial effect could be recapitulated by soluble products of this parasite, we tested an extract derived from T. gondii tachyzoites. Immunization of BALB/c mice with tachyzoites lysate antigen (TLA) elicited mixed Th1/Th2 responses. When TLA was applied together with the sensitizing ovalbumin (OVA), the development of allergic airway inflammation was reduced, with decreased airway hyperresponsiveness associated with reduced peribronchial and perivascular cellular infiltration, reduced production of OVA-specific Th2 cytokines in lungs and spleens and reduced levels of serum OVA-specific IgG1 as well as IgE-dependent basophil degranulation. Of note, TLA retained its immunomodulatory properties, inducing high levels of IL-6, TNFα, IL-10 and IL-12p70 in bone marrow-derived dendritic cells after heat-inactivation or proteinase K-treatment for disruption of proteins, but not after sodium metaperiodate-treatment that degrades carbohydrate structures, suggesting that carbohydrates may play a role in immunomodulatory properties of TLA. Here we show that extracts derived from parasites may replicate the benefits of parasitic infection, offering new therapies for immune-mediated disorders.
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http://dx.doi.org/10.1038/s41598-017-15663-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680314PMC
November 2017

Murine models for mucosal tolerance in allergy.

Semin Immunol 2017 04 12;30:12-27. Epub 2017 Aug 12.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address:

Immunity is established by a fine balance to discriminate between self and non-self. In addition, mucosal surfaces have the unique ability to establish and maintain a state of tolerance also against non-self constituents such as those represented by the large numbers of commensals populating mucosal surfaces and food-derived or air-borne antigens. Recent years have seen a dramatic expansion in our understanding of the basic mechanisms and the involved cellular and molecular players orchestrating mucosal tolerance. As a direct outgrowth, promising prophylactic and therapeutic models for mucosal tolerance induction against usually innocuous antigens (derived from food and aeroallergen sources) have been developed. A major theme in the past years was the introduction of improved formulations and novel adjuvants into such allergy vaccines. This review article describes basic mechanisms of mucosal tolerance induction and contrasts the peculiarities but also the interdependence of the gut and respiratory tract associated lymphoid tissues in that context. Particular emphasis is put on delineating the current prophylactic and therapeutic strategies to study and improve mucosal tolerance induction in allergy.
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http://dx.doi.org/10.1016/j.smim.2017.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100013PMC
April 2017

Enhanced and long term immunogenicity of a Her-2/neu multi-epitope vaccine conjugated to the carrier CRM197 in conjunction with the adjuvant Montanide.

BMC Cancer 2017 02 9;17(1):118. Epub 2017 Feb 9.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria.

Background: We previously identified three short single peptides (P4, P6 and P7) representing different B-cell epitopes on the extracellular domain of Her-2/neu for a vaccine that was tested in a phase-I clinical trial. Here we describe the improvement of the multi peptide vaccine by fusing the single peptides to a hybrid peptide P467.

Methods: After coupling to either virosomes or to diphtheria toxoid CRM197 (CRM), the hybrid peptide was tested in different concentrations in combination with either Montanide or Aluminium hydroxide (Alum) in preclinical studies.

Results: Already low amount (10 μg) of P467 conjugated to CRM led to faster onset of high antibody levels compared to the P467-virosome. The formulation P467-CRM-Montanide induced higher serum IgG antibody titers, compared with P467-CRM-Alum, as examined by ELISA using recombinant Her-2/neu or Her-2/neu natively expressed on the tumor cell line SK-BR-3. Compared to P467-CRM-Alum, higher in vitro production of IL-2 and IFNγ in the Montanide-immunized mice was induced after re-stimulation of splenocytes with CRM but also with P467, indicating a clear Th1-biased response. In contrast to the single B cell peptides, the hybrid peptide led to T cell proliferation and cytokine production as CD4 T cell epitopes were generated in the fusion region of the single peptides P4 and P6 or P6 and P7. Additionally, a significantly higher proportion IFNγ-producing CD8+ T cells was found in the P467-CRM-Montanide immunized mice, probably by Montanide-driven bystander activation. Importantly, anti-P467 IgG antibodies exhibited anti-tumor properties and the combination of anti-P467 specific IgG with Herceptin® was found to inhibit the proliferation of Her-2/neu-overexpressing cell line SK-BR-3 in a significantly higher capacity than Herceptin® alone.

Conclusions: Fusion of the B cell peptides has led to additional generation of CD4 T cell epitopes, and this P467-multi epitope vaccine was found to induce polyclonal antibody responses with anti-proliferative capacity against Her-2/neu. The hybrid vaccine together with Montanide induced higher and long-lasting antibody levels, Th1-biased cellular responses being superior to vaccination with the single B cell peptides. This vaccine formulation is now planned to be evaluated in a phase Ib/II study in Her-2/neu overexpressing cancer patients.
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http://dx.doi.org/10.1186/s12885-017-3098-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301331PMC
February 2017

[Guidelines for vaccination of immunocompromised individuals].

Wien Klin Wochenschr 2016 Aug 25;128 Suppl 4:337-76. Epub 2016 Jul 25.

Klinische Abteilung für Kinder- und Jugendheilkunde, Universitätsklinikum St. Pölten, St. Pölten, Österreich.

Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.
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http://dx.doi.org/10.1007/s00508-016-1033-6DOI Listing
August 2016

Universal Mass Vaccination Against Rotavirus: Indirect Effects on Rotavirus Infections in Neonates and Unvaccinated Young Infants Not Eligible for Vaccination.

J Infect Dis 2016 08 10;214(4):546-55. Epub 2016 May 10.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University Vienna.

Background: Rotavirus (RV)-associated infections account for high numbers of hospitalizations in neonates and young infants. Universal mass vaccination (UMV) has been shown to prevent the burden of disease in vaccinated children.

Methods: The present study investigated the long-term effects of UMV on RV-associated hospitalizations in children with particular focus on neonates and young infants (≤42 days old) not eligible for vaccination. Ten years of Austrian surveillance data were compared, including 10 960 laboratory-confirmed RV cases before (prevaccination period [PreVP]) and after (postvaccination period [PostVP]) introduction of UMV.

Results: A postvaccination decrease in hospitalized community-acquired RV infections by 89.3% was seen in all age groups, including unvaccinated neonates and young infants. Of the latter, 27.6% had a nosocomial RV infection in PreVP, and 19.3% in PostVP. Overall, the proportion of nosocomial RV infections increased from 5.5% in PreVP to 13.0% in PostVP. Breakthrough infections, usually after incomplete RV vaccination, could be identified in 6.2% of patients.

Conclusions: Unvaccinated neonates and infants ≤42 days old may indirectly benefit from UMV by reduction of RV infections. Breakthrough infections underline the importance of early and complete protection by the vaccine. In older patients, heightened awareness of nosocomial RV infections is warranted. Identification of RV reservoirs is also needed.
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http://dx.doi.org/10.1093/infdis/jiw186DOI Listing
August 2016

Oocyst-Derived Extract of Toxoplasma Gondii Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy.

PLoS One 2016 5;11(5):e0155081. Epub 2016 May 5.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria.

Introduction: Previously, we have shown that oral infection with Toxoplasma gondii oocysts prevented type I allergy in mice. Here we investigated whether the application of a T. gondii oocyst lysate antigen (OLA) could also reduce allergy development. BALB/c mice were immunised twice with OLA followed by sensitisation with the major birch pollen (BP) allergen Bet v 1 and an aerosol challenge with BP extract.

Methods: First, we tested OLA in vitro. Stimulation of splenocytes and bone marrow-derived dendritic cells (BMDC) with OLA led to the production of pro-inflammatory and regulatory cytokines such as IL-6, IFN-γ and IL-10. Moreover, BMDC exposed to OLA upregulated the maturation markers CD40, CD80, CD86, and MHCII. Furthermore, OLA was recognised by TLR2-transfected human embryonic kidney cells.

Results: Immunisation of mice with OLA induced high levels of Toxoplasma-specific IgG antibodies in sera along with increased production of IFN-γ and IL-10 in Toxoplasma-antigen restimulated splenocytes. OLA reduced allergic airway inflammation as manifested by significant reduction of eosinophils in bronchoalveolar fluids, decreased cellular infiltrates and mucus production in the lungs. Accordingly, Bet v 1-specific IgE was decreased in OLA-pretreated mice. The reduced allergic immune responses were accompanied by increased numbers of CD4+CD25highFoxp3+ regulatory T cells in spleens as well as by increased numbers of granulocytic myeloid-derived suppressor cells in lungs when compared to sensitised controls suggesting that these two cell populations might be involved in the suppression of the allergic immune responses.

Conclusion: Our data demonstrate that pretreatment with the oocyst extract can exert anti-allergic effects comparable to T. gondii infection. Thus, the immunomodulatory properties of the parasite extract indicate that this extract and in the future defined molecules thereof might serve as immunomodulatory adjuvants in allergy treatment and prophylaxis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155081PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857930PMC
July 2017

Primary vaccine failure to routine vaccines: Why and what to do?

Hum Vaccin Immunother 2016 ;12(1):239-43

a Institute of Specific Prophylaxis and Tropical Medicine; Medical University Vienna ; Vienna , Austria.

There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.
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http://dx.doi.org/10.1080/21645515.2015.1093263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962729PMC
December 2016

Comparable immune responsiveness but increased reactogenicity after subcutaneous versus intramuscular administration of tick borne encephalitis (TBE) vaccine.

Vaccine 2016 Apr 6;34(17):2027-34. Epub 2016 Jan 6.

Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria. Electronic address:

Evaluation of safety, immunogenicity and efficacy of vaccines during licensing studies is performed in relation to the selected vaccination route. For most adjuvanted vaccines, such as the TBE vaccine FSME-IMMUN, only intramuscular (i.m.) administration is licensed. Yet in certain situations, either because of medical indications, accidental application or due to a lack of sufficient muscular tissue, the vaccine might rather be applied subcutaneously (s.c.). With respect to the TBE vaccine there are currently however no data to support the use of the subcutaneous route of vaccination. In order to compare the reactogenicity and immune responsiveness upon i.m. and s.c. TBE vaccination 116 (58 females and 58 males) participants with a documented primary TBE vaccination course were randomized to receive either an i.m. or s.c. booster. Venous blood was collected before, 7 days, 1 month and 6 months after vaccination to determine antibody titer profiles. PBMC were isolated prior to and 7 days after booster to analyze lymphocyte subpopulations and cytokine production upon antigen restimulation. Subjects were monitored for the occurrence of side effects for 7 days post vaccination. Comparable levels of TBE specific neutralizing antibodies were induced after s.c. and i.m. vaccination. At the cellular level, IL-2, IFN gamma and IL-10 levels did not significantly differ using either route of vaccination and the distribution of T cell subsets was comparable along with a relative decrease of regulatory T-cells after both ways of administration. In contrast to the immunogenicity analyses, the data from safety diaries revealed a significantly higher rate of local, but not of systemic reactions after s.c. administration. In conclusion, this study demonstrates that both routes lead to comparable immune responses to the TBE antigen. The higher rate and intensity of local reactions, particularly among women, after s.c. vaccination however needs to be addressed during counseling.
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http://dx.doi.org/10.1016/j.vaccine.2015.12.057DOI Listing
April 2016

Genetic Variation of Bordetella pertussis in Austria.

PLoS One 2015 16;10(7):e0132623. Epub 2015 Jul 16.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132623PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504479PMC
April 2016