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首页> 外文期刊>Vaccine >Immune responses in the airways by nasal vaccination with systemic boosting against Pseudomonas aeruginosa in chronic lung disease
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Immune responses in the airways by nasal vaccination with systemic boosting against Pseudomonas aeruginosa in chronic lung disease

机译：在慢性肺部疾病中，通过鼻腔疫苗接种和全身免疫铜绿假单胞菌进行免疫应答

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RATIONALE: Pneumonia caused by Pseudomonas (P.) aeruginosa is a leading cause of morbidity and mortality in patients with chronic lung diseases. Systemic vaccination in patients with cystic fibrosis has been only successful in part. Mucosal vaccination could lead to enhanced airway immunogenicity. Pathogen specific secretory IgA antibodies could prevent bacterial invasion into the lung mucosa. OBJECTIVES: A phase 1-2 mucosal vaccination trial with an intranasal P. aeruginosa vaccine was performed. METHODS: 12 patients with chronic lung diseases (8 COPD, 2 cystic fibrosis, 1 bronchiectasis, 1 histiocytosis X) were vaccinated three times intranasally followed by a systemic booster vaccination with a recombinant hybrid protein encompassing the main protective epitopes of two outer membrane proteins of P. aeruginosa. Mucosal and systemic antibody responses were measured after boosting and after a half-year follow-up compared to a representative control cohort. MEASUREMENTS: Specific IgG and IgA antibodies in the patient's sera, saliva and sputum were determined by enzyme-linked immunosorbent assay (ELISA) and IgG subclass distributions were defined with monoclonal mouse antibodies. RESULTS: Both forms of vaccination were well tolerated. Significant elevated IgA and IgG antibodies could be measured in sputum, saliva and in the sera of 11/12 patients. CONCLUSIONS: Mucosal vaccination followed by systemic boost with an outer membrane protein vaccine against P. aeruginosa leads to airway immunogenicity against the pathogen. Further clinical trials should elucidate the protective efficacy of this vaccination method.
机译：理由：铜绿假单胞菌引起的肺炎是慢性肺病患者发病和死亡的主要原因。囊性纤维化患者的全身疫苗接种仅部分成功。粘膜疫苗接种可能导致气道免疫原性增强。病原体特异性分泌型IgA抗体可以防止细菌侵入肺粘膜。目的：进行了鼻内铜绿假单胞菌疫苗的1-2期粘膜疫苗接种试验。方法：对12例慢性肺疾病（8例慢性阻塞性肺病，2例囊性纤维化，1例支气管扩张，1例组织细胞增生症）进行鼻内疫苗接种3次，然后全身免疫接种重组杂合蛋白，该杂合蛋白包含两个外膜蛋白的主要保护表位铜绿假单胞菌。与典型对照组相比，加强免疫后和半年随访后测量粘膜和全身抗体应答。测量：通过酶联免疫吸附测定（ELISA）测定患者血清，唾液和痰中的特异性IgG和IgA抗体，并用单克隆小鼠抗体确定IgG亚类分布。结果：两种形式的疫苗接种均耐受良好。在11/12患者的痰液，唾液和血清中可检测到明显升高的IgA和IgG抗体。结论：粘膜疫苗接种，然后用针对铜绿假单胞菌的外膜蛋白疫苗全身加强免疫可导致针对病原体的气道免疫原性。进一步的临床试验应阐明这种疫苗接种方法的保护效力。

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