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载体结合的缺失变应原特异性 T 细胞表位的 Bet v 1 肽的预防性和治疗性疫苗接种通过阻断抗体在桦树花粉过敏的小鼠模型中减少 Bet v 1 特异性 T 细胞反应。

Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

机构信息

Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

出版信息

Clin Exp Allergy. 2014 Feb;44(2):278-87. doi: 10.1111/cea.12216.

DOI:10.1111/cea.12216
PMID:24447086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4215111/
Abstract

BACKGROUND

Vaccines consisting of allergen-derived peptides lacking IgE reactivity and allergen-specific T cell epitopes bound to allergen-unrelated carrier molecules have been suggested as candidates for allergen-specific immunotherapy.

OBJECTIVE

To study whether prophylactic and therapeutic vaccination with carrier-bound peptides from the major birch pollen allergen Bet v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T cell responses.

METHODS

Three Bet v 1-derived peptides, devoid of Bet v 1-specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies.

RESULTS

Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation.

CONCLUSION AND CLINICAL RELEVANCE

Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation.

摘要

背景

由缺乏 IgE 反应性和过敏原特异性 T 细胞表位的过敏原衍生肽与过敏原无关的载体分子组成的疫苗被认为是过敏原特异性免疫治疗的候选物。

目的

研究缺乏过敏原特异性 T 细胞表位的主要桦树花粉过敏原 Bet v 1 的载体结合肽的预防性和治疗性接种是否对 Bet v 1 特异性 T 细胞反应有影响。

方法

将 3 个缺乏 Bet v 1 特异性 T 细胞表位的 Bet v 1 衍生肽与 KLH 偶联,并吸附到氢氧化铝上,以获得特异性针对 Bet v 1 的过敏疫苗。用肽疫苗对 BALB/c 小鼠进行致敏前或致敏后免疫。通过 ELISA 分析 Bet v 1、KLH 和肽的特异性抗体反应。通过增殖试验研究了对 Bet v 1、KLH 和肽的 T 细胞和细胞因子反应。使用特异性抗体研究了肽特异性和过敏原特异性抗体对 T 细胞反应和过敏肺炎症的影响。

结果

载体结合的 Bet v 1 肽的预防性和治疗性接种诱导了 Bet v 1 特异性 IgG 抗体反应,而没有引发/增强 Bet v 1 特异性 T 细胞反应。肽疫苗对小鼠进行预防性和治疗性接种可诱导产生 Bet v 1 特异性抗体,抑制 Bet v 1 特异性 T 细胞反应和过敏肺炎症。

结论和临床相关性

用缺乏过敏原特异性 T 细胞表位的载体结合过敏原衍生肽进行免疫接种可诱导产生过敏原特异性 IgG 抗体,抑制过敏原特异性 T 细胞反应和过敏肺炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/4215111/ebcfa9d08e34/cea0044-0278-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/4215111/ebcfa9d08e34/cea0044-0278-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/4215111/66352d540234/cea0044-0278-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/4215111/efb005719dcb/cea0044-0278-f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/4215111/d1a83f73ec19/cea0044-0278-f7.jpg
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