Prevention of allergy by virus-like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model

Kratzer Bernhard; Koehler Cordula; Hofer Sandra; Smole Ursula; Trapin Doris; Iturri Jagoba; Pum Dietmar; Kienzl Philip; Elbe-Buerger Adelheid; Gattinger Pia; Mittermann Irene; Linhart Birgit; Gadermaier Gabriele; Jahn-Schmid Beatrice; Neunkirchner Alina; Valenta Rudolf; Pickl Winfried F.

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Prevention of allergy by virus-like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model

机译：用病毒样纳米粒子（VNP）预防过敏（VNP）在人源鼠过敏模型中递送屏蔽版的主要过敏原

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Background In high-risk populations, allergen-specific prophylaxis could protect from sensitization and subsequent development of allergic disease. However, such treatment might itself induce sensitization and allergies, thus requiring hypoallergenic vaccine formulations. We here characterized the preventive potential of virus-like nanoparticles (VNP) expressing surface-exposed or shielded allergens. Methods Full-length major mugwort pollen allergen Art v 1 was selectively targeted either to the surface or to the inner side of the lipid bilayer envelope of VNP. Upon biochemical and immunological analysis, their preventive potential was determined in a humanized mouse model of mugwort pollen allergy. Results Virus-like nanoparticles expressing shielded version of Art v 1, in contrast to those expressing surface-exposed Art v 1, were hypoallergenic as they hardly induced degranulation of rat basophil leukemia cells sensitized with Art v 1-specific mouse or human IgE. Both VNP versions induced proliferation and cytokine production of allergen-specific T cells in vitro. Upon intranasal application in mice, VNP expressing surface-exposed but not shielded allergen induced allergen-specific antibodies, including IgE. Notably, preventive treatment with VNP expressing shielded allergen-protected mice from subsequent sensitization with mugwort pollen extract. Protection was associated with a Th1/Treg-dominated cytokine response, increased Foxp3(+) Treg numbers in lungs, and reduced lung resistance when compared to mice treated with empty particles. Conclusion Virus-like nanoparticles represent a novel and versatile platform for the in vivo delivery of allergens to selectively target T cells and prevent allergies without inducing allergic reactions or allergic sensitization.

机译：背景技术在高风险群体中，过敏原特异性预防可以免受过敏性疾病的敏化和随后的发育。然而，这种治疗本身可能诱导致敏和过敏，因此需要低过敏性疫苗制剂。我们在这里表征了表达表面暴露或屏蔽过敏原的病毒样纳米颗粒（VNP）的预防性。方法全长主要Mugwort花粉过敏原v 1选择性地靶向VNP的脂质双层包络的表面或内侧。生物化学和免疫学分析后，在Mugwort Pollen过敏的人源化小鼠模型中测定了预防潜力。结果表达屏蔽版的病毒样纳米颗粒，与表达表面暴露的艺术v 1相反，它们是低变的，因为它们几乎没有诱导用艺术v 1特异性小鼠或人Ige致敏的大鼠嗜碱性白血病细胞的升级。 VNP版本诱导体外过敏原特异性T细胞的增殖和细胞因子产生。在小鼠鼻内应用后，表达表面暴露但未屏蔽过敏原诱导过敏原特异性抗体，包括IgE。值得注意的是，用随后用Mugwort Pollen提取物的随后致敏表达VNP的预防治疗屏蔽过敏原小鼠。与用空颗粒处理的小鼠相比，保护与Th1 / Treg标准的细胞因子响应，增加Foxp3（+）Treg数增加，降低肺阻力。结论病毒样纳米粒子代表了一种新颖和通用的平台，用于体内递送过敏原，以选择性靶向T细胞并防止过敏性而不引起过敏反应或过敏性敏化。

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来源
《Allergy》 |2019年第2期|共15页
作者
Kratzer Bernhard; Koehler Cordula; Hofer Sandra; Smole Ursula; Trapin Doris; Iturri Jagoba; Pum Dietmar; Kienzl Philip; Elbe-Buerger Adelheid; Gattinger Pia; Mittermann Irene; Linhart Birgit; Gadermaier Gabriele; Jahn-Schmid Beatrice; Neunkirchner Alina; Valenta Rudolf; Pickl Winfried F.;
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作者单位

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

Univ Nat Resources &

Life Sci Vienna Inst Biophys Dept Nanobiotechnol Vienna Austria;

Univ Nat Resources &

Life Sci Vienna Inst Biophys Dept Nanobiotechnol Vienna Austria;

Med Univ Vienna Div Immunol Allergy &

Infect Dis Dept Dermatol Vienna Austria;

Med Univ Vienna Div Immunol Allergy &

Infect Dis Dept Dermatol Vienna Austria;

Med Univ Vienna Dept Pathophysiol &

Allergy Res Ctr Pathophysiol Infectiol &

Immunol Vienna;

Med Univ Vienna Dept Pathophysiol &

Allergy Res Ctr Pathophysiol Infectiol &

Immunol Vienna;

Med Univ Vienna Dept Pathophysiol &

Allergy Res Ctr Pathophysiol Infectiol &

Immunol Vienna;

Univ Salzburg Div Allergy &

Immunol Dept Biosci Salzburg Austria;

Med Univ Vienna Dept Pathophysiol &

Allergy Res Ctr Pathophysiol Infectiol &

Immunol Vienna;

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

Med Univ Vienna Dept Pathophysiol &

Allergy Res Ctr Pathophysiol Infectiol &

Immunol Vienna;

Med Univ Vienna Inst Immunol Ctr Pathophysiol Infectiol &

Immunol Lazarettgasse 19 A-1090;

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原文格式 PDF
正文语种 eng
中图分类医学免疫学;
关键词
allergy prevention; mugwort pollen allergy; Treg cells; virus-like nanoparticles; prevention; lung APC;

机译：过敏预防;Mugwort花粉过敏;Treg细胞;病毒样纳米粒子;预防;肺部APC;

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专利

1. Prevention of allergy by virus-like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model [J] . Kratzer Bernhard, Koehler Cordula, Hofer Sandra, Allergy . 2019,第2期

机译：用病毒样纳米粒子（VNP）预防过敏（VNP）在人源鼠过敏模型中递送屏蔽版的主要过敏原
2. Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type I allergy. [J] . Wiedermann U, Jahn Schmid-B, Bohle B, The Journal of Allergy and Clinical Immunology . 1999,第6期

机译：在I型变态反应的鼠模型中，通过鼻内或口服施用重组投注v 1（主要的桦树花粉变应原）来抑制抗原特异性T细胞和B细胞反应。
3. Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens [J] . The Journal of Allergy and Clinical Immunology . 2020,第4期

机译：基于工程病毒样粒子的疫苗对花生过敏术语显示单个主要花生过敏原
4. Dust mite allergens: A major risk factor in development of allergies in Dubai [C] . Sultan D.M., Khalil M.M. European Multicolloquium of Parasitology Congress . 2012

机译：尘埃螨过敏原：迪拜过敏发展的主要危险因素
5. Using BALB/c mice as a model of food allergy to study gene expression profiles in response to common food allergens. [D] . Husain, Mainul. 2010

机译：使用BALB / c小鼠作为食物过敏的模型来研究对常见食物过敏原的基因表达谱。
6. Prevention of allergy by virus‐like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model [O] . Bernhard Kratzer, Cordula Köhler, Sandra Hofer, -1

机译：通过病毒样纳米颗粒（VNP）预防过敏在人源化鼠类过敏模型中提供主要过敏原的屏蔽版本
7. Prevention of allergy by virus-like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model [O] . Bernhard Kratzer, Cordula Köhler, Sandra Hofer, 2018

机译：用病毒样纳米粒子（VNP）预防过敏（VNP）在人源鼠过敏模型中提供屏蔽版的主要过敏原

Prevention of allergy by virus-like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model

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