Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF.
Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF.
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DOI：
10.1016/j.vaccine.2010.12.087
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发表时间：
2011-03-03
期刊：
影响因子：
5.5
通讯作者：
Worgall, Stefan
中科院分区：
文献类型：
--
作者：
Krause, Anja;Whu, Wen Zhu;Xu, Yaqin;Joh, Ju;Crystal, Ronald G.;Worgall, Stefan
复制缺陷腺病毒（Ad）载体是抗铜绿假单胞菌引起的肺部感染疫苗的一个有吸引力的平台。基于非人类血清型的Ad载体已经被开发出来，以规避人类预先存在的抗Ad免疫的问题。本研究分析了抗p。表达铜绿假单胞菌外膜蛋白F （AdC7OprF）的非人灵长类AdC7载体诱导铜绿假单胞菌全身和肺粘膜免疫与人血清型Ad5OprF载体免疫小鼠相比，肌肉注射AdC7OprF诱导小鼠血清和粘膜抗oprf IgG水平相似，肺上皮衬液（ELF）中抗oprf IgA水平升高（p < 0.05）。与Ad5OprF相比，AdC7OprF免疫后，oprf脉冲同源脾树突状细胞（DC）刺激的脾T细胞中oprf特异性INF-γ与Ad5OprF相似（p < 0.05）。相比之下，与Ad5OprF相比，AdC7OprF免疫后，脾脏或肺DC刺激的肺T细胞中oprf特异性INF-γ反应增加（p<0.05）。有趣的是，与Ad5OprF免疫相比，呼吸道直接给药AdC7OprF导致血清中oprf特异性IgG，肺ELF中oprf特异性IgG和IgA以及肺t细胞中oprf特异性INF-γ的增加，并在致命剂量的P. aeruginosa攻击后存活。这些数据表明，与基于ad5的载体免疫相比，基于adc7的疫苗载体免疫全身或肺粘膜可诱导更强的肺体液和细胞抗转基因免疫，并且有利于adc7载体作为诱导肺粘膜免疫的疫苗。
Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P.aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p>0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p>0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p<0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity.
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