Reisinger Jürgen, Horak Friedrich, Pauli Gabrielle, van Hage Marianne, Cromwell Oliver, König Franz, Valenta Rudolf, Niederberger Verena
Department of Otorhinolaryngology, Center for Physiology and Pathophysiology, Vienna General Hospital, Vienna, Austria.
J Allergy Clin Immunol. 2005 Aug;116(2):347-54. doi: 10.1016/j.jaci.2005.04.003.
We have performed a double-blind, placebo-controlled injection immunotherapy study with genetically modified derivatives of the major birch pollen allergen, Bet v 1 (Bet v 1-trimer, Bet v 1-fragments).
To investigate whether vaccination with genetically modified allergens induces allergen-specific antibodies in nasal secretions and to study whether these antibodies affect nasal allergen sensitivity.
A randomly picked subgroup of patients (n = 23; placebo, n = 10; trimer, n = 10; fragments, n = 3) was subjected to an extensive analysis of serum samples and nasal lavage fluids and to nasal provocation testing. Bet v 1-specific IgG(1-4) and IgA antibodies were determined in serum samples obtained before and after vaccination, after the birch pollen season, and 1 year after start of vaccination as well as in nasal lavage fluids obtained after the birch pollen season and 1 year after start of vaccination by ELISA. Nasal sensitivity to natural, birch pollen-derived Bet v 1 was determined by active anterior rhinomanometry after the birch pollen season and 1 year after start of vaccination.
Vaccination with genetically modified Bet v 1 derivatives, but not with placebo, induced Bet v 1-specific IgG1, IgG2, and IgG4, and low IgA antibodies in serum, which also appeared in nasal secretions, but no IgG3 antibodies. The levels of therapy-induced Bet v 1-specific IgG4 antibodies in nasal secretions were significantly (P < .05) associated with reduced nasal sensitivity to natural, birch pollen-derived Bet v 1 as objectively determined by controlled nasal provocation experiments.
Our data demonstrate that vaccination with genetically modified allergens induces IgG antibody responses against the corresponding natural allergen not only in serum but also in mucosal fluids, where they may protect against allergen-induced inflammation.
我们开展了一项双盲、安慰剂对照的注射免疫疗法研究，使用主要桦树花粉过敏原Bet v 1的基因改造衍生物（Bet v 1三聚体、Bet v 1片段）。
研究用基因改造过敏原进行疫苗接种是否能在鼻分泌物中诱导产生过敏原特异性抗体，并研究这些抗体是否会影响鼻过敏原敏感性。
随机挑选一组患者（n = 23；安慰剂组，n = 10；三聚体组，n = 10；片段组，n = 3），对其血清样本和鼻灌洗液进行广泛分析，并进行鼻激发试验。通过酶联免疫吸附测定法（ELISA），测定接种疫苗前后、桦树花粉季节后以及开始接种疫苗1年后获得的血清样本中以及桦树花粉季节后和开始接种疫苗1年后获得的鼻灌洗液中Bet v 1特异性IgG(1 - 4)和IgA抗体。在桦树花粉季节后和开始接种疫苗1年后，通过主动前鼻测压法测定对天然桦树花粉来源的Bet v 1的鼻敏感性。
用基因改造的Bet v 1衍生物接种疫苗可诱导血清中产生Bet v 1特异性IgG1、IgG2和IgG4以及低水平IgA抗体，这些抗体也出现在鼻分泌物中，但未诱导产生IgG3抗体。通过对照鼻激发试验客观测定，鼻分泌物中治疗诱导的Bet v 1特异性IgG4抗体水平与对天然桦树花粉来源的Bet v 1的鼻敏感性降低显著相关（P < .05）。
我们的数据表明，用基因改造过敏原进行疫苗接种不仅能在血清中，还能在黏膜液中诱导针对相应天然过敏原的IgG抗体反应，这些抗体可能预防过敏原诱导的炎症。
