36 results on '"Westritschnig K"'
Search Results
2. Recombinant allergen–based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation
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Gadermaier, E., Staikuniene, J., Scheiblhofer, S., Thalhamer, J., Kundi, M., Westritschnig, K., Swoboda, I., Flicker, S., and Valenta, R.
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- 2011
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3. Immunoglobulin E antibody reactivity to bacterial antigens in atopic dermatitis patients
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Reginald, K., Westritschnig, K., Werfel, T., Heratizadeh, A., Novak, N., Focke-Tejkl, M., Hirschl, A. M., Leung, D. Y. M., Elisyutina, O., Fedenko, E., and Valenta, R.
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- 2011
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4. Immunotherapy of Allergic Disease
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Valenta, R., primary, Ball, T., additional, Focke, M., additional, Linhart, B., additional, Mothes, N., additional, Niederberger, V., additional, Spitzauer, S., additional, Swoboda, I., additional, Vrtala, S., additional, Westritschnig, K., additional, and Kraft, D., additional
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- 2004
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5. Different allergenic activity of grass pollen allergens revealed by skin testing
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Westritschnig, K., Horak, F., Swoboda, I., Balic, N., Spitzauer, S., Kundi, M., Fiebig, H., Suck, R., Cromwell, O., and Valenta, R.
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- 2008
6. A comparative analysis of the cross-reactivity in the polcalcin family including Syr v 3, a new member from lilac pollen
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Ledesma, A., Barderas, R., Westritschnig, K., Quiralte, J., Pascual, C. Y., Valenta, R., Villalba, M., and Rodríguez, R.
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- 2006
7. Analysis of the sensitization profile towards allergens in central Africa
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Westritschnig, K., Sibanda, E., Thomas, W., Auer, H., Aspöck, H., Pittner, G., Vrtala, S., Spitzauer, S., Kraft, D., and Valenta, R.
- Published
- 2003
8. Allergy / Recombinant allergen-based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation
- Author
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Gadermaier, E., Staikuniene, J., Scheiblhofer, S., Thalhamer, J., Kundi, M., Westritschnig, K., Swoboda, Ines, Flicker, S., and Valenta, R.
- Published
- 2011
9. European journal of clinical investigation / Different allergenic activity of grass pollen allergens revealed by skin testing
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Westritschnig, K., Horak, F., Swoboda, Ines, Balic, N., Spitzauer, S., Kundi, M., Fiebig, H., Suck, R., Cromwell, O., and Valenta, R.
- Published
- 2008
10. Immunoglobulin E antibody reactivity to bacterial antigens in atopic dermatitis patients
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Reginald, K., primary, Westritschnig, K., additional, Werfel, T., additional, Heratizadeh, A., additional, Novak, N., additional, Focke-Tejkl, M., additional, Hirschl, A. M., additional, Leung, D. Y. M., additional, Elisyutina, O., additional, Fedenko, E., additional, and Valenta, R., additional
- Published
- 2010
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11. Recombinant allergens for the diagnosis of type I allergy.
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Westritschnig K, Kraft D, and Valenta R
- Published
- 2002
12. Identification of cross-reactive and genuine Parietaria judaica pollen allergens
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Stumvoll, S., Westritschnig, K., Lidholm, J., Spitzauer, S., Colombo, P., Duro, G., Kraft, D., Geraci, D., and Valenta, R.
- Abstract
Background:: The weed Parietaria judaica is one of the most important pollen allergen sources in the Mediterranean area. Objective:: We sought to identify P judaica pollen allergen, which might be used to serologically distinguish genuine Parietaria sensitization and cross-reactivity to allergens from other weed species (eg, mugwort and ragweed). Methods:: The allergen profile of P judaica IgE-reactive sera from weed pollen-sensitized allergic individuals from the Mediterranean region (n=36) with high Parietaria pollen exposure and from weed pollen-allergic patients with little or no Parietaria exposure (Austria, n=42; Scandinavia, n=8; United States, n=19) was established by CAP FEIA measurements and by IgE immunoblot inhibition experiments with recombinant allergens. Results:: The majority (83%) of the Mediterranean weed pollen-allergic patients mounted high IgE antibody levels (mean specific IgE, 20.89 kUA/L) against recombinant (r) Par j 2, whereas only 7% of the non-Mediterranean weed-allergic patients showed low IgE reactivity to rPar j 2 (mean specific IgE, 1.03 kUA/L). The cytoskeletal protein profilin and a 2-EF-hand calcium-binding allergen were identified as cross-reactive Parietaria allergens, which were recognized preferentially by Parietaria-positive, non-Mediterranean weed pollen-allergic patients. Conclusion:: rPar j 2 might be used as a diagnostic marker allergen to identify weed pollen-allergic patients who are genuinely sensitized against Parietaria pollen and thus would be particularly suited for specific immunotherapy with Parietaria pollen extract.
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- 2003
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13. STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia.
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Morozzi G, Rothen J, Toussaint G, De Lange K, Westritschnig K, Doelemeyer A, Ueberschlag VP, Kahle P, Lambert C, Obrecht M, Beckmann N, Ritter V, Panesar M, Stauffer D, Garnier I, Mueller M, Guerini D, Keller CG, Knehr J, Roma G, Bidinosti M, Brachat S, Morvan F, and Fornaro M
- Abstract
Inflammatory responses are crucial for regeneration following peripheral nerve injury (PNI). PNI triggers inflammatory responses at the site of injury. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream effector stimulator of interferon genes (STING) sense foreign and self-DNA and trigger type I interferon (IFN) immune responses. We demonstrate here that following PNI, the cGAS/STING pathway is upregulated in the sciatic nerve of naive rats and dysregulated in old rats. In a nerve crush mouse model where STING is knocked out, myelin content in sciatic nerve is increased resulting in accelerated functional axon recovery. STING KO mice have lower macrophage number in sciatic nerve and decreased microglia activation in spinal cord 1 week post injury. STING activation regulated processing of colony stimulating factor 1 receptor (CSF1R) and microglia survival in vitro . Taking together, these data highlight a previously unrecognized role of STING in the regulation of nerve regeneration., Competing Interests: All authors are employees and some are shareholders of Novartis., (© 2021 The Authors.)
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- 2021
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14. Vaccination of nonallergic individuals with recombinant hypoallergenic fragments of birch pollen allergen Bet v 1: Safety, effects, and mechanisms.
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Campana R, Marth K, Zieglmayer P, Weber M, Lupinek C, Zhernov Y, Elisyutina O, Khaitov M, Rigler E, Westritschnig K, Berger U, Wolkersdorfer M, Horak F Jr, Horak F, and Valenta R
- Subjects
- Adolescent, Adult, Allergens adverse effects, Allergens genetics, Allergens immunology, Antigens, Plant adverse effects, Antigens, Plant genetics, Antigens, Plant immunology, Double-Blind Method, Female, Humans, Immunoglobulin E immunology, Immunoglobulin G immunology, Male, Recombinant Proteins administration & dosage, Recombinant Proteins adverse effects, Young Adult, Allergens administration & dosage, Antigens, Plant administration & dosage, Betula immunology, Pollen immunology, Rhinitis, Allergic, Seasonal prevention & control, Vaccination adverse effects
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- 2019
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15. Immunogenicity of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children From a Japanese Encephalitis Virus-endemic Region.
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Dubischar KL, Kadlecek V, Sablan JB, Borja-Tabora CF, Gatchalian S, Eder-Lingelbach S, Kiermayr S, Spruth M, and Westritschnig K
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- Adolescent, Child, Child, Preschool, Dengue Virus immunology, Humans, Infant, Japanese Encephalitis Vaccines administration & dosage, Seroepidemiologic Studies, Antibodies, Viral blood, Encephalitis Virus, Japanese immunology, Encephalitis, Japanese prevention & control, Japanese Encephalitis Vaccines immunology
- Abstract
Background: Japanese encephalitis (JE) is a major public health concern in Asia and poses a small but potentially fatal threat to travelers from nonendemic countries, including children. No JE vaccine for pediatric use has been available in Europe and the United States., Methods: Age-stratified cohorts of children between 2 months and 17 years received 2 doses of Vero cell-derived inactivated JE virus vaccine (IXIARO; Valneva Austria GmbH, Vienna, Austria) administered 28 days apart [<3 years, 0.25 mL (half adult dose); ≥3 years, 0.5 mL (full adult dose)]. Immunogenicity endpoints were seroconversion rate, 4-fold increase in JE neutralizing antibody titer and geometric mean titer assessed 56 days and 7 months after the first vaccination in 496 subjects of the intent-to-treat population. The immune response to JE virus at both time points was also analyzed according to prevaccination JE virus and dengue virus serostatus., Results: At day 56, seroconversion was attained in ≥99.2% of subjects with age-appropriate dosing, 4-fold increases in titer were reported for 77.4%-100% in various age groups, and geometric mean titers ranged from 176 to 687, with younger children having the strongest immune response. At month 7, seroconversion was maintained in 85.5%-100% of subjects. Pre-existing JE virus immunity did not impact on immune response at day 56; however, it led to a better persistence of protective antibody titers at month 7., Conclusions: IXIARO is highly immunogenic at both doses tested in the pediatric population, leading to protective antibody titers at day 56 in >99% of subjects who received the age-appropriate dose.
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- 2017
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16. Safety of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children: An Open-label, Randomized, Active-controlled, Phase 3 Study.
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Dubischar KL, Kadlecek V, Sablan B Jr, Borja-Tabora CF, Gatchalian S, Eder-Lingelbach S, Mueller Z, and Westritschnig K
- Subjects
- Adolescent, Antibodies, Viral, Child, Child, Preschool, Encephalitis, Japanese immunology, Humans, Infant, Japanese Encephalitis Vaccines administration & dosage, Japanese Encephalitis Vaccines immunology, Encephalitis, Japanese prevention & control, Japanese Encephalitis Vaccines adverse effects
- Abstract
Background: Japanese encephalitis remains a serious health concern in Asian countries and has sporadically affected pediatric travelers. In the present study, we monitored the safety profile of the Japanese encephalitis virus vaccine IXIARO (Valneva Austria GmbH, Vienna, Austria) in a pediatric population., Methods: We randomized 1869 children between 2 months and 17 years of age in an age-stratified manner to vaccination with IXIARO or one of the control vaccines, Prevnar (formerly Wyeth Pharmaceuticals Inc., now Pfizer Inc., Kent, United Kingdom) and HAVRIX 720 (GlaxoSmithKline Biologicals, Rixensart, Belgium). Adverse events (AEs) (unsolicited and solicited local and systemic AEs), serious AEs and medically attended AEs were assessed up to day 56 and month 7 after the first dose., Results: Incidences of AEs, serious AEs or medically attended AEs did not differ significantly between the groups in any age stratum. AEs were most frequent in children <1 year of age and decreased with age. AEs of special interest, predefined as AEs associated with potential hypersensitivity/allergy or neurologic disorders up to day 56, were reported in 4.6% (IXIARO) versus 6.3% (Prevnar) in the ≥2 months to <1 year age group and 3.4% (IXIARO) versus 3.3% (HAVRIX) in the ≥1 to <18 years age group. Fever, the most frequent systemic reaction in 23.7% of infants to 3.8% of adolescents, decreased with age and did not differ between groups., Conclusions: The safety profile of IXIARO was comparable to the control vaccines in terms of overall AE rates, serious AEs and medically attended AEs.
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- 2017
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17. A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients.
- Author
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Rello J, Krenn CG, Locker G, Pilger E, Madl C, Balica L, Dugernier T, Laterre PF, Spapen H, Depuydt P, Vincent JL, Bogár L, Szabó Z, Völgyes B, Máñez R, Cakar N, Ramazanoglu A, Topeli A, Mastruzzo MA, Jasovich A, Remolif CG, Del Carmen Soria L, Andresen Hernandez MA, Ruiz Balart C, Krémer I, Molnár Z, von Sonnenburg F, Lyons A, Joannidis M, Burgmann H, Welte T, Klingler A, Hochreiter R, and Westritschnig K
- Subjects
- Adult, Aged, Double-Blind Method, Female, Humans, Intensive Care Units organization & administration, Male, Middle Aged, Placebos, Pseudomonas Infections drug therapy, Pseudomonas Vaccines therapeutic use, Pseudomonas aeruginosa pathogenicity, Respiration, Artificial methods, Sepsis prevention & control, Pseudomonas Infections prevention & control, Pseudomonas Vaccines pharmacology
- Abstract
Background: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients., Methods: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days., Results: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups., Conclusion: This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns., Trial Registration: ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.
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- 2017
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18. Immunogenicity and safety of the inactivated Japanese encephalitis vaccine IXIARO® in elderly subjects: Open-label, uncontrolled, multi-center, phase 4 study.
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Cramer JP, Dubischar K, Eder S, Burchard GD, Jelinek T, Jilma B, Kollaritsch H, Reisinger E, and Westritschnig K
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- Aged, Aged, 80 and over, Antibodies, Viral blood, Austria, Female, Germany, Humans, Immunization, Secondary, Japanese Encephalitis Vaccines adverse effects, Japanese Encephalitis Vaccines immunology, Male, Prospective Studies, Seroconversion, Encephalitis, Japanese prevention & control, Immunogenicity, Vaccine, Japanese Encephalitis Vaccines therapeutic use
- Abstract
Background: IXIARO® is a Vero cell-derived, inactivated Japanese encephalitis (JE) vaccine licensed mainly in western countries for children and adults traveling to JE endemic areas. Limited immunogenicity and safety data in elderly travelers have been available., Objectives: To evaluate safety and immunogenicity of IXIARO in elderly subjects., Methods: Open-label, single arm, multi-centered study. Two-hundred subjects with good general health, including adequately controlled chronic conditions, received two doses of IXIARO®, 28days apart. Protective levels of antibodies were tested 42days after the second dose. Systemic and local adverse events (AEs) were solicited for 7days after each dose, unsolicited AEs were collected up to day 70 and in a phone call at month 7., Summary of Results: Subjects were aged 64-83years (median 69.0years). Nineteen percent of subjects had serious or medically attended AEs up to Day 70 (primary endpoint), none of them causally linked to IXIARO. Solicited local AEs were reported by 33.5% (most common: local tenderness) and solicited systemic AEs by 27% (most common: headache) of subjects. The seroprotection rate was 65% with a geometric mean titre (GMT) of 37. Subjects with tick borne encephalitis (TBE) vaccinations in the past 5years (N=29) had a SCR of 90% and GMT of 65., Conclusions: IXIARO is generally well tolerated in the elderly, and the safety profile is largely comparable with younger adults. SCR and GMT are lower compared to younger adults, but SCR is in the range reported in elderly for other vaccines e.g. against TBE, hepatitis-A virus (HAV)/hepatitis-B virus (HBV), influenza. The differences in SCR and GMT from younger to elderly adults were in the range of other vaccines. Duration of protection is uncertain in older persons, therefore a booster dose (third dose) should be considered before any further exposure to JE virus., (Copyright © 2016. Published by Elsevier Ltd.)
- Published
- 2016
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19. Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers.
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Bézay N, Ayad A, Dubischar K, Firbas C, Hochreiter R, Kiermayr S, Kiss I, Pinl F, Jilma B, and Westritschnig K
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- Adjuvants, Immunologic administration & dosage, Adult, Aged, Alum Compounds administration & dosage, Anti-Bacterial Agents adverse effects, Antibodies, Bacterial blood, Clostridioides difficile, Diarrhea chemically induced, Dose-Response Relationship, Immunologic, Female, Humans, Immunization, Secondary, Male, Middle Aged, Neutralization Tests, Recombinant Proteins immunology, Young Adult, Bacterial Proteins immunology, Bacterial Toxins immunology, Bacterial Vaccines therapeutic use, Clostridium Infections prevention & control, Enterotoxins immunology
- Abstract
Background: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea and colitis and the most common pathogen of health care-associated infections. In the US, CDI causes approximately half a million infections and close to 30,000 deaths. Despite antibiotic treatment of C. difficile associated diarrhoea, the disease is complicated by its recurrence in up to 30% of patients., Methods: An open-label, partially randomized, dose-escalation Phase I trial was performed in two parts. Sixty volunteers aged ≥18 to <65 years were randomized into five treatment groups to receive three immunizations (Day 0, 7, 21) of VLA84 (20μg with Alum, 75μg with or without Alum, 200μg with or without Alum). Eighty-one volunteers aged ≥65 were randomized into four treatment groups (75μg with or without Alum, 200μg with or without Alum) and received four immunizations (Day 0, 7, 28 and 56). All subjects were followed for safety and immunogenicity for six months., Results: VLA84 was safe and well tolerated. Fifty-one adult volunteers (85%) and 50 elderly (62%) experienced at least one solicited or unsolicited adverse event (AE). Forty-eight adult volunteers (80%) and 40 elderly (49%) experienced related AEs which were mostly mild or moderate. No related serious adverse event and no death occurred. The vaccine induced high antibody titres against Toxin A and Toxin B in both study populations., Conclusion: VLA84 was safe, well tolerated and highly immunogenic in adult volunteers aged ≥18 to <65 years and elderly volunteers aged ≥65 years. This study is registered at ClinicalTrials.gov under registration number NCT01296386., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
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- 2016
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20. A randomized, placebo-controlled phase I study assessing the safety and immunogenicity of a Pseudomonas aeruginosa hybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers.
- Author
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Westritschnig K, Hochreiter R, Wallner G, Firbas C, Schwameis M, and Jilma B
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- Adolescent, Adult, Antibodies, Bacterial blood, Bacterial Proteins genetics, Female, Healthy Volunteers, Humans, Immunoglobulin G blood, Injections, Intramuscular, Lipoproteins genetics, Male, Middle Aged, Placebos administration & dosage, Pseudomonas Vaccines administration & dosage, Pseudomonas Vaccines genetics, Pseudomonas aeruginosa genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Vaccination adverse effects, Vaccination methods, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic adverse effects, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, Young Adult, Bacterial Proteins immunology, Lipoproteins immunology, Pseudomonas Vaccines adverse effects, Pseudomonas Vaccines immunology, Pseudomonas aeruginosa immunology
- Abstract
Introduction: IC43 is a recombinant outer membrane protein-based vaccine against Pseudomonas aeruginosa (P. aeruginosa) consisting of OprF- and OprI- epitopes (Opr, outer membrane protein; OprF/I, OprF/OprI hybrid vaccine) with an N-terminal His 6 tag (Met-Ala-(His)6-OprF190-342-OprI21-83)., Objectives: The study aimed to confirm the optimal dose of IC43 in adults with regard to immunogenicity, safety, and tolerability after vaccination with three different dosages of IC43, compared with placebo, and to investigate a potential immune-enhancing effect of the adjuvant, aluminum hydroxide. Subjects were randomly allocated in a 1:1:1:1:1 ratio to one of five treatment groups: 50, 100, or 200 µg IC43 with adjuvant, 100 µg IC43 without adjuvant, or placebo (0.9% sodium chloride) and two intramuscular injections were given in the deltoid region 7 d apart., Results: The primary immunogenicity analysis of OprF/I-specific IgG antibody titers on day 14 demonstrated statistically significant differences among treatment groups (P<0.0001), with a significantly higher immune response detected in each IC43 treatment group compared with placebo. From day 0 to day 14, a ≥4-fold increase in OprF/I-specific immunoglobulin G (IgG) antibody titers were observed in>90% of subjects in all IC43 treatment groups in the per-protocol (PP) and intention-to-treat (ITT) populations; a ≥50-fold titer increase was observed in 42.6% subjects including all IC43 treatment groups. On day 90, OprF/I-specific IgGs started to decline in all IC43 treatment groups but remained significantly higher until 6 mo compared with placebo. Assessment of functional antibody induction by opsonophagocytic assay (OPA) followed a similar pattern compared with OprF/I-specific IgG kinetics. At day 14, a ≥2-fold increase in OPA titer was observed in 54.5% subjects within all IC43 treatment groups. An increase in antibody avidity index was observed after the second vaccination. At day 14, >96% of subjects in each IC43 treatment group had detectable OprF/I-specific IgG antibodies. Anti-histidine IgG antibody titers peaked on day 14 and were reduced on day 90 in all IC43 treatment groups. OprF/I-specific IgG secreted by antibody-secreting cell (ASC) was detected in all IC43 groups by B-cell ELIspot after the second vaccination and up to 6 mo. All vaccinations were safe and well tolerated up to the maximum cumulative dosage of 400 µg IC43., Conclusion: IC43 doses equal to or greater than 50 µg were sufficient to induce a plateau of IgG antibody responses in healthy volunteers. Higher doses, whether adjuvanted or non-adjuvanted, were not more effective., Methods: In this phase I, randomized, placebo-controlled, observer-blinded, multicenter clinical trial, 163 healthy volunteers (18-65 y) were randomly assigned to five treatment groups (1:1:1:1:1). Three groups received IC43 with adjuvant: 50 µg (n=32), 100 µg (n=33), or 200 µg (n=33). One group received IC43 100 µg without adjuvant (n=32), and one group received placebo (0.9% sodium chloride) (n=33). Each subject received two intramuscular vaccinations, separated by a 7-d interval (days 0 and 7) (Fig. 1). Humoral immune response was assessed by measurement of outer membrane protein F/I (OprF/I)-specific antibodies determined by enzyme-linked immunosorbent assay (ELISA), anti-histidine antibodies determined by ELISA, and functional antibody activity determined by opsonophagocytic assay (OPA), up to 6 mo post-vaccination. Antibody avidity was measured on days 7 and 14 from samples that had detectable vaccine antibody-specific immunoglobulin G (IgG) antibody titers. At the Austrian site only, the B-cell ELIspot assay was used to determine specific ASC responses. Safety was assessed using adverse event monitoring and clinical laboratory tests. Local and systemic tolerability was recorded in a subject diary for 7 d after each vaccination and by investigators up to 6 mo post-vaccination.
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- 2014
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21. Efficacy of a travelers' diarrhea vaccine system in travelers to India.
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Steffen R, Cramer JP, Burchard G, Jelinek T, Schwarz U, Ramdas P, Chatterjee S, Jiang ZD, DuPont HL, Dewasthaly S, Westritschnig K, and Behrens RH
- Subjects
- Administration, Cutaneous, Adolescent, Adult, Diarrhea ethnology, Diarrhea microbiology, Double-Blind Method, Escherichia coli Infections ethnology, Escherichia coli Infections microbiology, Female, Germany epidemiology, Humans, Incidence, India ethnology, Male, Middle Aged, Treatment Outcome, United Kingdom epidemiology, Young Adult, Bacterial Vaccines administration & dosage, Diarrhea prevention & control, Escherichia coli immunology, Escherichia coli Infections prevention & control, Travel
- Abstract
Background: A patch vaccine containing heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) has demonstrated to be beneficial in reducing the rate and severity of travelers' diarrhea in Latin America. To evaluate the efficacy of this transdermal vaccine system in an area with a different diarrheal pathogen profile, an additional phase 2 study was conducted in European travelers to India., Methods: For this multicenter, randomized, double-blinded, placebo-controlled field study 723 subjects were recruited; 603 (299 LT vaccine, 304 placebo) were included in the per-protocol-population (PPP)., Results: Although the LT patch induced a measurable LT immune response in recipients, it failed to protect against LT ETEC or all-cause diarrhea. In the PPP the incidence rate of diarrhea as per primary endpoint was 6.0% (18 of 299) in the vaccine group and 5.9% (18 of 304) in the placebo group. Additionally, lower than expected rates of LT ETEC diarrheas were observed in India. The vaccine delivery system frequently produced rash and pruritus at the site of application, long term hyperpigmentation persisted in a minority of LT recipients, and also few site reactions were noted in the placebo group., Conclusions: The evaluated patch vaccine failed to satisfy mainly with respect to protective efficacy. Noninvasive prophylactic agents against travelers' diarrhea, particularly vaccines against the most frequent pathogens, thus continue to be badly needed., (© 2013 International Society of Travel Medicine.)
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- 2013
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22. Antigen processing and presentation by dendritic cells is independent of coronin 1.
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Westritschnig K, BoseDasgupta S, Tchang V, Siegmund K, and Pieters J
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- Adoptive Transfer, Animals, Antigen Presentation genetics, Bone Marrow Cells immunology, Bone Marrow Cells metabolism, Bone Marrow Cells microbiology, Dendritic Cells metabolism, Dendritic Cells microbiology, Female, Flow Cytometry, Listeria monocytogenes immunology, Lymphocyte Count, Male, Mice, Mice, Knockout, Microfilament Proteins deficiency, Microfilament Proteins immunology, Ovalbumin genetics, Ovalbumin immunology, Recombinant Proteins genetics, Recombinant Proteins immunology, T-Lymphocytes metabolism, T-Lymphocytes microbiology, T-Lymphocytes transplantation, Antigen Presentation immunology, Dendritic Cells immunology, Gene Expression Regulation immunology, Microfilament Proteins genetics, T-Lymphocytes immunology
- Abstract
Coronin 1, which is a member of the evolutionary conserved coronin protein family that is highly expressed in all leukocytes is involved in the activation of the Ca(2+)/calcineurin signaling pathway following cell surface stimulation in T cells, B cells as well as macrophages. Mice deficient for coronin 1 have strongly reduced peripheral T cell numbers as a result of a lack of pro-survival signals for naïve T cells. Whether or not impaired antigen processing and presentation in the absence of coronin 1 expression contributes to this reduction of T cell numbers is unknown. We here show that coronin 1-deficient bone marrow-derived dendritic cells develop normally, and that wild type and coronin 1-deficient dendritic cells were equally able to induce antigen-specific proliferation of T cells. Furthermore, upon immunization, in vivo proliferation of adoptively transferred antigen-specific T cells was comparable in wild type and coronin 1-deficient mice. Finally, infection of wild type and coronin 1-deficient dendritic cells with an ovalbumin-expressing Listeria monocytogenes strain induced comparable levels of ovalbumin-specific T cells responses. Together these results suggest that coronin 1 is dispensable for antigen processing and presentation by dendritic cells., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
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- 2013
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23. Staphylococcus aureus fibronectin-binding protein specifically binds IgE from patients with atopic dermatitis and requires antigen presentation for cellular immune responses.
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Reginald K, Westritschnig K, Linhart B, Focke-Tejkl M, Jahn-Schmid B, Eckl-Dorna J, Heratizadeh A, Stöcklinger A, Balic N, Spitzauer S, Niederberger V, Werfel T, Thalhamer J, Weidinger S, Novak N, Ollert M, Hirschl AM, and Valenta R
- Subjects
- Adhesins, Bacterial genetics, Adolescent, Adult, Aged, Amino Acid Sequence, Animals, Base Sequence, Child, Child, Preschool, Dermatitis, Atopic microbiology, Female, Humans, Infant, Male, Mice, Middle Aged, Molecular Sequence Data, Recombinant Proteins immunology, Superantigens immunology, Young Adult, Adhesins, Bacterial immunology, Antigen Presentation immunology, Dermatitis, Atopic immunology, Immunoglobulin E immunology, Staphylococcal Infections immunology, Staphylococcus aureus immunology
- Abstract
Background: Staphylococcus aureus superinfections occur in more than 90% of patients with atopic dermatitis (AD) and aggravate skin inflammation. S aureus toxins lead to tissue damage and augment T-cell-mediated skin inflammation by a superantigen effect., Objective: To characterize IgE-reactive proteins from S aureus., Methods: A genomic S aureus library was screened with IgE from patients with AD for DNA clones coding for IgE-reactive antigens. One was identified as fibronectin-binding protein (FBP). Recombinant FBP was expressed in Escherichia coli, purified, and tested for specific IgE reactivity in patients with AD. Its allergenic activity was studied in basophil activation experiments and T-cell cultures. The in vivo allergenic activity was investigated by sensitizing mice., Results: Using IgE from patients with AD for screening of a genomic S aureus library, an IgE-reactive DNA clone was isolated that coded for FBP. Recombinant FBP was expressed in E coli and purified. It reacted specifically with IgE from patients with AD and exhibited allergenic activity in basophil degranulation assays. FBP showed specific T-cell reactivity requiring antigen presentation and induced the secretion of proinflammatory cytokines from PBMCs. Mice sensitized with FBP mounted FBP-specific IgE responses, showed FBP-specific basophil degranulation as well as FBP-specific T-cell proliferation, and mixed T(h)2/T(h)1 cytokine secretion., Conclusion: Evidence is provided that specific humoral and cellular immune responses to S aureus antigens dependent on antigen presentation represent a novel mechanism for S aureus-induced skin inflammation in AD. Furthermore, FBP may be used for the development of novel diagnostic and therapeutic strategies for S aureus infections., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
- Published
- 2011
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24. A combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived surface protein VP1 and a nonallergenic peptide of the major timothy grass pollen allergen Phl p 1.
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Edlmayr J, Niespodziana K, Linhart B, Focke-Tejkl M, Westritschnig K, Scheiblhofer S, Stoecklinger A, Kneidinger M, Valent P, Campana R, Thalhamer J, Popow-Kraupp T, and Valenta R
- Subjects
- Animals, Cross Reactions immunology, Electrophoresis, Polyacrylamide Gel, Humans, Immunoglobulin E immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Mice, Rabbits, Recombinant Fusion Proteins immunology, Rhinovirus, Vaccines, Combined immunology, Allergens immunology, Common Cold prevention & control, Hypersensitivity prevention & control, Plant Proteins immunology, Vaccines, Synthetic immunology, Viral Proteins immunology
- Abstract
Allergens and rhinovirus infections are among the most common elicitors of respiratory diseases. We report the construction of a recombinant combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived VP1, the surface protein which is critically involved in infection of respiratory cells, and a nonallergenic peptide of the major grass pollen allergen Phl p 1. Recombinant hybrid molecules consisting of VP1 and a Phl p 1-derived peptide of 31 aa were expressed in Escherichia coli. The hybrid molecules did not react with IgE Abs from grass pollen allergic patients and lacked allergenic activity when exposed to basophils from allergic patients. Upon immunization of mice and rabbits, the hybrids did not sensitize against Phl p 1 but induced protective IgG Abs that cross-reacted with group 1 allergens from different grass species and blocked allergic patients' IgE reactivity to Phl p 1 as well as Phl p 1-induced basophil degranulation. Moreover, hybrid-induced IgG Abs inhibited rhinovirus infection of cultured human epithelial cells. The principle of fusing nonallergenic allergen-derived peptides onto viral carrier proteins may be used for the engineering of safe allergy vaccines which also protect against viral infections.
- Published
- 2009
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25. Three-dimensional structure of the cross-reactive pollen allergen Che a 3: visualizing cross-reactivity on the molecular surfaces of weed, grass, and tree pollen allergens.
- Author
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Verdino P, Barderas R, Villalba M, Westritschnig K, Valenta R, Rodriguez R, and Keller W
- Subjects
- Allergens genetics, Allergens immunology, Allergens metabolism, Amino Acid Sequence, Antigens, Plant immunology, Antigens, Plant metabolism, Betula chemistry, Calcium-Binding Proteins genetics, Calcium-Binding Proteins immunology, Calcium-Binding Proteins metabolism, Chenopodium album chemistry, Cross Reactions, Crystallization, Immunoglobulin E metabolism, Molecular Sequence Data, Plant Proteins genetics, Plant Proteins immunology, Plant Proteins metabolism, Poaceae chemistry, Pollen chemistry, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins immunology, Recombinant Proteins metabolism, Surface Properties, Allergens chemistry, Antigens, Plant chemistry, Betula immunology, Calcium-Binding Proteins chemistry, Chenopodium album immunology, Plant Proteins chemistry, Poaceae immunology, Pollen immunology
- Abstract
Two EF-hand calcium-binding allergens (polcalcins) occur in the pollen of a wide variety of unrelated plants as highly cross-reactive allergenic molecules. We report the expression, purification, immunological characterization, and the 1.75-A crystal structure of recombinant Che a 3 (rChe a 3), the polcalcin from the weed Chenopodium album. The three-dimensional structure of rChe a 3 resembles an alpha-helical fold that is essentially identical with that of the two EF-hand allergens from birch pollen, Bet v 4, and timothy grass pollen, Phl p 7. The extensive cross-reactivity between Che a 3 and Phl p 7 is demonstrated by competition experiments with IgE Abs from allergic patients as well as specific Ab probes. Amino acid residues that are conserved for the two EF-hand allergen family were identified in multiple sequence alignments of polcalcins from 15 different plants. Next, the three-dimensional structures of rChe a 3, rPhl p 7, and rBet v 4 were used to identify conserved amino acids with high surface exposition to visualize surface patches as potential targets for the polyclonal IgE Ab response of allergic patients. The essentially identical three-dimensional structures of rChe a 3, rPhl p 7, and rBet v 4 explain the extensive cross-reactivity of allergic patients IgE Abs with two EF-hand allergens from unrelated plants. In addition, analyzing the three-dimensional structures of cross-reactive Ags for conserved and surface exposed amino acids may be a first approach to mapping the conformational epitopes on disease-related Ags that are recognized by polyclonal patient Abs.
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- 2008
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26. Immunogold electron microscopic localization of the 2 EF-hand calcium-binding pollen allergen Phl p 7 and its homologues in pollens of grasses, weeds and trees.
- Author
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Grote M, Westritschnig K, and Valenta R
- Subjects
- Allergens metabolism, Allergens ultrastructure, Antibodies physiology, Antigens, Plant, Asteraceae ultrastructure, Calcium-Binding Proteins immunology, Calcium-Binding Proteins ultrastructure, Humans, Immunohistochemistry, Microscopy, Immunoelectron, Phleum ultrastructure, Pollen metabolism, Pollen ultrastructure, Protein Binding immunology, Protein Structure, Tertiary, Trees ultrastructure, Allergens immunology, Asteraceae immunology, Calcium-Binding Proteins metabolism, EF Hand Motifs immunology, Phleum immunology, Pollen immunology, Structural Homology, Protein, Trees immunology
- Abstract
Background: The 2 EF-hand calcium-binding allergen from timothy grass pollen, Phl p 7, contains the majority of relevant IgE epitopes among calcium-binding allergens occurring in pollen species of different plants., Objective: To describe the ultrastructural localization of Phl p 7 allergen in timothy grass pollen and its homologues in a broad spectrum of allergologically relevant pollens from grasses (timothy grass, rye grass), trees (birch, alder, olive) and weeds (mugwort, ribwort, ragweed) commonly growing in Europe., Materials and Methods: Mature pollens from 8 different plant species were collected and anhydrously prepared for transmission electron microscopy. In ultrathin sections, allergens were localized using an antibody prepared against a Phl p 7-derived peptide comprising the C-terminal half of the Phl p 7 wild-type molecule in combination with a secondary antibody coupled to 10-nm colloidal gold particles., Results: Phl p 7 and Phl p 7 homologues were detected in pollen from each of the 8 pollen species investigated. The allergens were found in the cytoplasm of the pollen grains (cytoplasmic matrix, mitochondria, nuclei) and in the pollen wall (preferably the exine). Reserve materials were unlabeled., Conclusions: The 2 EF-hand calcium-binding allergen Phl p 7 from timothy grass and its homologues can be localized in all pollen species under investigation. This finding confirms that Phl p 7 is a marker allergen for sensitization of patients to a novel family of 2 EF-hand calcium-binding pollen allergens occurring in a number of important allergenic plants in Europe., ((c) 2008 S. Karger AG, Basel.)
- Published
- 2008
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27. Mast cell-derived proteases control allergic inflammation through cleavage of IgE.
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Rauter I, Krauth MT, Westritschnig K, Horak F, Flicker S, Gieras A, Repa A, Balic N, Spitzauer S, Huss-Marp J, Brockow K, Darsow U, Behrendt H, Ring J, Kricek F, Valent P, and Valenta R
- Subjects
- Allergens adverse effects, Allergens metabolism, Female, Humans, Hypersensitivity etiology, Hypersensitivity, Immediate etiology, Hypersensitivity, Immediate immunology, Mast Cells immunology, Receptors, IgE metabolism, Skin immunology, Hypersensitivity immunology, Immunoglobulin E metabolism, Inflammation immunology, Mast Cells enzymology, Tryptases metabolism
- Abstract
Background: Cross-linking of mast cell-bound IgE releases proinflammatory mediators, cytokines, and proteolytic enzymes and is a key event in allergic inflammation., Objective: We sought to study the effect of proteases released on effector cell activation on receptor-bound IgE and their possible role in the regulation of allergic inflammation., Methods: Using molar ratios of purified recombinant tryptase and human IgE, we studied whether tryptase can cleave IgE. Similar experiments were performed with mast cell lysates in the presence or absence of protease inhibitors. IgE cleavage products were detected in supernatants of allergen cross-linked, cultivated mast cells and in tissue fluids collected from patients' skin after IgE-mediated degranulation. The effects of protamine, an inhibitor of heparin-dependent proteases on IgE-mediated allergic in vivo skin inflammation in human subjects were studied., Results: We show that beta-tryptase, a major protease released during mast cell activation, cleaves IgE. IgE degradation products were detected in tryptase-containing tissue fluids collected from sites of allergic inflammation. The biologic significance of this mechanism is demonstrated by in vivo experiments showing that protease inhibition enhances allergic skin inflammation., Conclusion: We suggest that IgE cleavage by effector cell proteases is a natural mechanism for controlling allergic inflammation.
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- 2008
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28. A hypoallergenic vaccine obtained by tail-to-head restructuring of timothy grass pollen profilin, Phl p 12, for the treatment of cross-sensitization to profilin.
- Author
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Westritschnig K, Linhart B, Focke-Tejkl M, Pavkov T, Keller W, Ball T, Mari A, Hartl A, Stöcklinger A, Scheiblhofer S, Thalhamer J, Ferreira F, Vieths S, Vogel L, Böhm A, Valent P, and Valenta R
- Subjects
- Allergens chemistry, Allergens genetics, Anti-Allergic Agents chemistry, Antibodies chemistry, Antibodies genetics, Antibodies immunology, Antibody Specificity genetics, Antibody Specificity immunology, Antigen-Antibody Reactions, Antigens, Plant chemistry, Antigens, Plant genetics, Binding Sites, Circular Dichroism, Epitopes immunology, Genetic Engineering methods, Histamine immunology, Humans, Immunoglobulin E blood, Immunoglobulin E immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Models, Molecular, Pollen chemistry, Pollen genetics, Polymerase Chain Reaction, Profilins chemistry, Profilins genetics, Protein Structure, Secondary, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics, Sensitivity and Specificity, T-Lymphocytes immunology, Vaccines chemistry, Vaccines genetics, Allergens immunology, Anti-Allergic Agents immunology, Antigens, Plant immunology, Pollen immunology, Profilins immunology, Recombinant Fusion Proteins immunology, Vaccines immunology
- Abstract
Profilins are highly cross-reactive allergens in pollens and plant food. In a paradigmatic approach, the cDNA coding for timothy grass pollen profilin, Phl p 12, was used as a template to develop a new strategy for engineering an allergy vaccine with low IgE reactivity. Non-IgE-reactive fragments of Phl p 12 were identified by synthetic peptide chemistry and restructured (rs) as a new molecule, Phl p 12-rs. It comprised the C terminus of Phl p 12 at its N terminus and the Phl p 12 N terminus at its C terminus. Phl p 12-rs was expressed in Escherichia coli and purified to homogeneity. Determination of secondary structure by circular dichroism indicated that the restructuring process had reduced the IgE-reactive alpha-helical contents of the protein but retained its beta-sheet conformation. Phl p 12-rs exhibited reduced IgE binding capacity and allergenic activity but preserved T cell reactivity in allergic patients. IgG Abs induced by immunization of mice and rabbits with Phl p 12-rs cross-reacted with pollen and food-derived profilins. Recombinant Phl p 12-rs, rPhl p 12-rs, induced less reaginic IgE to the wild-type allergen than rPhl p 12. However, the rPhl p 12-rs-induced IgGs inhibited allergic patients' IgE Ab binding to profilins to a similar degree as those induced by immunization with the wild type. Phl p 12-rs specific IgG inhibited profilin-induced basophil degranulation. In conclusion, a restructured recombinant vaccine was developed for the treatment of profilin-allergic patients. The strategy of tail-to-head reassembly of hypoallergenic allergen fragments within one molecule represents a generally applicable strategy for the generation of allergy vaccines.
- Published
- 2007
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29. Allergen cleavage by effector cell-derived proteases regulates allergic inflammation.
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Rauter I, Krauth MT, Flicker S, Gieras A, Westritschnig K, Vrtala S, Balic N, Spitzauer S, Huss-Marp J, Brockow K, Darsow U, Ring J, Behrendt H, Semper H, Valent P, and Valenta R
- Subjects
- Allergens chemistry, Amino Acid Sequence, Animals, Betula, Cell Degranulation, Cell Line, Tumor, Humans, Mast Cells metabolism, Molecular Sequence Data, Phleum, Plant Proteins chemistry, Plant Proteins metabolism, Pollen, Protamines metabolism, Rats, Tryptases, Allergens metabolism, Inflammation metabolism, Serine Endopeptidases metabolism
- Abstract
The key event of allergic inflammation, allergen-induced crosslinking of mast cell-bound IgE antibodies, is accompanied by release of inflammatory mediators, cytokines, and proteases, in particular beta-tryptase. We provide evidence that protease-mediated cleavage of allergens represents a mechanism that regulates allergen-induced mast cell activation. When used in molar ratios as they occur in vivo, purified beta-tryptase cleaved major grass and birch pollen allergens, resulting in defined peptide fragments as mapped by mass spectrometry. Tryptase-cleaved allergens showed reduced IgE reactivity and allergenic activity. The biological relevance is demonstrated by the fact that lysates from activated human mast cells containing tryptase levels as they occur in vivo cleaved allergens. Additionally, protamine, an inhibitor of heparin-dependent effector cell proteases, augmented allergen-induced release of mediators from effector cells. Protease-mediated allergen cleavage may represent an important mechanism for terminating allergen-induced effector cell activation.
- Published
- 2006
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30. Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7.
- Author
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Westritschnig K, Focke M, Verdino P, Goessler W, Keller W, Twardosz A, Mari A, Horak F, Wiedermann U, Hartl A, Thalhamer J, Sperr WR, Valent P, and Valenta R
- Subjects
- Allergens chemistry, Allergens immunology, Allergens metabolism, Animals, Anti-Allergic Agents administration & dosage, Anti-Allergic Agents chemical synthesis, Anti-Allergic Agents immunology, Antigens, Plant, Basophils immunology, Basophils metabolism, Binding Sites, Antibody genetics, Binding, Competitive immunology, Calcium-Binding Proteins chemistry, Calcium-Binding Proteins immunology, Calcium-Binding Proteins metabolism, Cell Degranulation, Cell Line, Tumor, Cross Reactions, Dose-Response Relationship, Immunologic, Histamine Release immunology, Humans, Immunoglobulin E metabolism, Immunoglobulin G biosynthesis, Immunoglobulin G metabolism, Mice, Mutagenesis, Site-Directed, Peptide Fragments administration & dosage, Peptide Fragments genetics, Peptide Fragments immunology, Peptide Fragments metabolism, Phleum chemistry, Phleum genetics, Plant Proteins chemistry, Plant Proteins immunology, Plant Proteins metabolism, Pollen genetics, Pollen immunology, Rabbits, Rats, Skin Tests, Structure-Activity Relationship, Vaccines administration & dosage, Vaccines immunology, Allergens genetics, Calcium-Binding Proteins genetics, Desensitization, Immunologic methods, Phleum immunology, Plant Proteins genetics, Vaccines chemical synthesis, Vaccines genetics
- Abstract
The grass pollen allergen, Phl p 7, belongs to a family of highly cross-reactive calcium-binding pollen allergens. Because Phl p 7 contains most of the disease-eliciting epitopes of pollen-derived calcium-binding allergens, hypoallergenic variants were engineered according to the x-ray crystal structure of Phl p 7 for allergy vaccination. In three recombinant variants, amino acids essential for calcium binding were mutated, and two peptides comprising the N- and C-terminal half were obtained by synthetic peptide chemistry. As determined by circular dichroism analysis and size exclusion chromatography coupled to mass spectrometry, recombinant mutants showed altered structural fold and lacked calcium-binding capacity, whereas the two synthetic peptides had completely lost their structural fold. Allergic patients' IgE Ab binding was strongest reduced to the variant containing two mutations in each of the two calcium-binding sites and to the peptides. Basophil histamine release and skin test experiments in allergic patients identified the peptides as the vaccine candidates with lowest allergenic activity. Immunization of rabbits with the peptides induced IgG Abs that blocked allergic patients' IgE binding to Phl p 7 and inhibited allergen-induced basophil degranulation. Our results indicate that disruption of an allergen's three-dimensional structure represents a general strategy for the generation of hypoallergenic allergy vaccines, and demonstrate the importance of allergen-specific IgG Abs for the inhibition of immediate allergic symptoms.
- Published
- 2004
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31. Tree pollen allergens.
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Mothes N, Westritschnig K, and Valenta R
- Subjects
- Allergens adverse effects, Cross Reactions, Desensitization, Immunologic, Humans, Hypersensitivity, Immediate diagnosis, Hypersensitivity, Immediate etiology, Hypersensitivity, Immediate therapy, Pollen adverse effects, Trees adverse effects, Allergens classification, Pollen classification, Trees classification
- Published
- 2004
32. Can we genetically engineer safer and more effective immunotherapy reagents?
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Westritschnig K and Valenta R
- Subjects
- Antigens genetics, Antigens immunology, Humans, Immunoglobulin E immunology, Immunotherapy, Active methods, Recombinant Proteins genetics, Recombinant Proteins immunology, Desensitization, Immunologic methods, Hypersensitivity therapy
- Abstract
Purpose of Review: Progress in allergen-specific immunotherapy, the only causative form of allergy treatment, was limited by the lack of defined allergen molecules for vaccine formulation. Today the genetic informations for the most common allergens have been obtained. Here we review recombinant allergen-based technologies for the improvement of diagnosis and therapy of allergy., Recent Findings: Numerous strategies, including the genetic engineering of allergens for reduction of allergenic activity, have been developed to improve allergen-specific immunotherapy. Genetically modified allergen derivatives with reduced allergenic activity, preserved T cell epitope repertoire and retained immunogenicity have been characterized in vitro and in vivo., Summary: Based on the review of the recently published data we argue that it is possible to genetically engineer safer and more effective immunotherapy reagents.
- Published
- 2003
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33. Three-dimensional structure of the panallergen Phl p 7.
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Verdino P, Westritschnig K, Valenta R, and Keller W
- Subjects
- Antigens, Plant, Crystallography, X-Ray, Dimerization, Allergens chemistry, Calcium-Binding Proteins chemistry
- Published
- 2003
- Full Text
- View/download PDF
34. The cross-reactive calcium-binding pollen allergen, Phl p 7, reveals a novel dimer assembly.
- Author
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Verdino P, Westritschnig K, Valenta R, and Keller W
- Subjects
- Amino Acid Sequence, Antigens, Plant, Dimerization, Drug Design, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Alignment, Sequence Homology, Amino Acid, Vaccines, Allergens chemistry, Calcium-Binding Proteins chemistry, Phleum chemistry, Plant Proteins chemistry
- Abstract
The timothy grass pollen allergen Phl p 7 assembles most of the IgE epitopes of a novel family of 2 EF-hand calcium-binding proteins and therefore represents a diagnostic marker allergen and vaccine candidate for immunotherapy. Here we report the first three-dimensional structure of a representative of the 2 EF-hand allergen family, Phl p 7, in the calcium-bound form. The protein occurs as a novel dimer assembly with unique features: in contrast to well known EF-hand proteins such as calmodulin, parvalbumin or the S100 proteins, Phl p 7 adopts an extended conformation. Two protein monomers assemble in a head-to-tail arrangement with domain-swapped EF-hand pairing. The intertwined dimer adopts a barrel-like structure with an extended hydrophobic cavity providing a ligand-binding site. Calcium binding acts as a conformational switch between an open and a closed dimeric form of Phl p 7. These findings are interesting in the context of lipid- and calcium-dependent pollen tube growth. Furthermore, the structure of Phl p 7 allows for the rational development of vaccine strategies for treatment of sensitized allergic patients.
- Published
- 2002
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35. Different IgE reactivity profiles in birch pollen-sensitive patients from six European populations revealed by recombinant allergens: an imprint of local sensitization.
- Author
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Movérare R, Westritschnig K, Svensson M, Hayek B, Bende M, Pauli G, Sorva R, Haahtela T, Valenta R, and Elfman L
- Subjects
- Adolescent, Adult, Aged, Allergens genetics, Antibody Specificity, Antigens, Plant, Asthma immunology, Calcium-Binding Proteins genetics, Calcium-Binding Proteins immunology, Child, Conjunctivitis, Allergic immunology, Europe, Female, Humans, Immunoblotting, Male, Middle Aged, Plant Proteins genetics, Plant Proteins immunology, Recombinant Proteins immunology, Allergens immunology, Betula immunology, Immunoglobulin E immunology, Pollen immunology, Rhinitis, Allergic, Seasonal immunology
- Abstract
Background: Sensitivity to birch pollen allergens is a common feature among European patients with seasonal pollen allergy. In this in vitro study, we examined the specific serum IgE binding profiles to individual birch pollen allergens in birch-sensitive patients from six European populations., Methods: The study included 242 patients from Finland, Sweden, Austria, France, Switzerland and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their sera were analyzed for specific IgE reactivity to individual birch pollen allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen extract using Pharmacia CAP System and immunoblotting., Results: Almost all Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (>or=98%). Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65 and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%) and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more common in the other populations (20-43%). Reactivity to Bet v 4 was rare in all populations (5-11%) except for the Italian patients, in whom 3 of 11 sera were positive (27%). The immunoblot results supported the specific IgE profiles obtained with Pharmacia CAP System showing a broader IgE reactivity profile in patients from central and southern Europe as compared to northern Europe., Conclusion: Component-resolved allergy diagnosis with recombinant allergens reveals that the IgE reactivity profiles to individual birch pollen allergens vary between European populations. This observation may be explained by sensitization to different allergen sources and will have an impact on allergen-specific prevention and therapy strategies., (Copyright 2002 S. Karger AG, Basel)
- Published
- 2002
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36. Molecular, structural, and immunologic relationships between different families of recombinant calcium-binding pollen allergens.
- Author
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Tinghino R, Twardosz A, Barletta B, Puggioni EM, Iacovacci P, Butteroni C, Afferni C, Mari A, Hayek B, Di Felice G, Focke M, Westritschnig K, Valenta R, and Pini C
- Subjects
- Amino Acid Sequence, Cross Reactions, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin E blood, Models, Molecular, Molecular Sequence Data, Poaceae adverse effects, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins immunology, Sequence Alignment, Structure-Activity Relationship, Trees adverse effects, Allergens adverse effects, Allergens chemistry, Allergens genetics, Allergens immunology, Calcium metabolism, Hypersensitivity etiology, Poaceae immunology, Pollen adverse effects, Pollen chemistry, Pollen genetics, Pollen immunology, Trees immunology
- Abstract
Background: Calcium-binding plant allergens can be grouped in different families according to the number of calcium-binding domains (EF hands)., Objective: We sought to identify pollens containing crossreactive calcium-binding allergens and to investigate structural and immunologic similarities of members belonging to different families of calcium-binding allergens., Methods: By means of multiple sequence alignment and molecular modeling, we searched for structural similarities among pollen allergens with 2 (Phl p 7, timothy grass; Aln g 4, alder), 3 (Bet v 3, birch) and 4 EF hands (Jun o 4, prickly juniper). Purified recombinant Aln g 4 and Jun o 4 were used to determine the prevalence of IgE recognition in 210 patients sensitized to different pollens and to search, by means of ELISA competition, for the presence of cross-reactive epitopes in pollens from 16 unrelated plant species. IgE cross-reactivity among the allergen families was studied with purified rPhl p 7, rAln g 4, rBet v 3, and rJun o 4 and 2 synthetic peptides comprising the N-terminal and C-terminal EF hands of Phl p 7 by means of ELISA competition., Results: Structural similarities were found by using molecular modeling among the allergens with 2, 3, and 4 EF hands. Pollens from 16 unrelated plants contained Aln g 4- and Jun o 4-related epitopes. Twenty-two percent of the patients with multiple pollen sensitization reacted to at least one of the calcium-binding allergens. A hierarchy of IgE cross-reactivity (rPhl p7 > rAln g 4 > rJun o 4 > rBet v 3) could be established that identified rPhl p 7 as the EF-hand allergen containing most IgE epitopes in the population studied., Conclusion: The demonstration that members of different families of calcium-binding plant allergens share similarities suggests that it may be possible to use representative molecules for the diagnosis and therapy of allergies to EF-hand allergens.
- Published
- 2002
- Full Text
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