Nasal immunization with Burkholderia multivorans outer membrane proteins and the mucosal adjuvant adamantylamide dipeptide confers efficient protection against experimental lung infections with B. multivorans and B. cenocepacia
Nasal immunization with Burkholderia multivorans outer membrane proteins and the mucosal adjuvant adamantylamide dipeptide confers efficient protection against experimental lung infections with B. multivorans and B. cenocepacia
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DOI：
10.1128/iai.01668-06
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Grinstein, Saul
中科院分区：
文献类型：
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作者：
Bertot, Gustavo M.;Restelli, Marcela A.;Grinstein, Saul
机会性病原体（例如铜绿假单胞菌和洋葱伯克霍尔德菌复合体成员）引起的慢性肺部感染是囊性纤维化患者发病和死亡的主要原因。革兰氏阴性细菌的外膜蛋白（OMP）是有前途的候选疫苗抗原。在这项研究中，我们评估了小鼠鼻内接种 B. multivorans 的 OMP 和粘膜佐剂金刚酰胺二肽 (AdDP) 所带来的免疫原性、保护性和交叉保护。用来自 B. multivorans 和 B. cenocepacia 的 OMP 加上 AdDP 对幼稚动物进行疫苗接种，刺激了强大的粘膜和全身免疫反应。使用慢性肺部感染的小鼠模型，我们观察到接种疫苗的动物肺部清除 B. multivorans 的能力增强，这与 OMP 特异性分泌性免疫球蛋白 A 反应相关。此外，OMP 免疫小鼠在用多食芽孢杆菌进行细菌攻击后，肺部感染迅速消退，几乎没有出现肺部病变。此外，我们证明，在该小鼠感染模型中，施用多食伯克霍尔德杆菌 OMP 疫苗可提供针对洋葱伯克霍尔德杆菌攻击的保护，这表明 OMP 提供针对洋葱伯克霍尔德杆菌复合体的交叉保护。因此，我们得出结论，通过鼻内接种 OMPs 加 AdDP 引发的对多食伯克霍尔德杆菌的粘膜免疫可以预防多食伯克霍尔德氏菌的早期定植和感染，并且还可以改善肺组织损伤，同时引发针对新洋葱伯克霍尔德氏菌的交叉保护。这些结果支持这样的观点：增加气道粘膜免疫力的疗法可能对囊性纤维化患者有帮助。
Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.