Vaccination against Pseudomonas aeruginosa pneumonia in immunocompromised mice.
Vaccination against Pseudomonas aeruginosa pneumonia in immunocompromised mice.
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免疫功能低下小鼠的铜绿假单胞菌肺炎疫苗接种。
DOI：
10.1128/cvi.00419-07
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Goldberg,JoannaB
中科院分区：
文献类型：
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作者：
Scarff,JenniferM;Goldberg,JoannaB
免疫功能低下的患者极易感染铜绿假单胞菌。我们的实验室先前表明，鼻内施用表达 P. 的减毒沙门氏菌菌株。铜绿糖脂多糖 O 抗原可有效清除野生型小鼠鼻内攻击后的细菌并预防死亡。我们有兴趣研究这种疫苗策略对免疫受损小鼠的功效。分别用环磷酰胺 (Cy) 或 RB6-8C5 抗体腹膜内治疗导致白细胞减少或中性粒细胞减少的小鼠对 P 更敏感。与未治疗的小鼠相比，铜绿脓毒症肺炎的50%致死剂量比野生型小鼠低几个对数。这种超敏性还与 Cy 小鼠的肝脏和脾脏细菌传播以及肺通透性增加有关。与载体免疫小鼠相比，治疗前接种疫苗的小鼠存活率更高，细菌载量更低。尽管治疗对抗体滴度没有影响，但这种保护水平仍然低于未治疗的疫苗接种小鼠的保护水平。在细菌递送时将抗体直接施用到感染部位可以延长免疫功能低下小鼠的存活时间并降低细菌负荷。这些结果证明了白细胞的重要性，同时仍然表明抗体在预防疟原虫中发挥着关键作用。铜绿假单胞菌感染。
Immunocompromised patients are highly susceptible to infection withPseudomonas aeruginosa. Our laboratory previously showed that intranasal administration of an attenuatedSalmonellastrain expressing theP. aeruginosalipopolysaccharide O antigen was effective in clearing bacteria and preventing mortality in wild-type mice after intranasal challenge. We were interested in investigating the efficacy of this vaccine strategy in immunocompromised mice. Mice rendered leukopenic or neutropenic by intraperitoneal treatment with cyclophosphamide (Cy) or RB6-8C5 antibody, respectively, were more susceptible toP. aeruginosapneumonia than their nontreated counterparts, demonstrating 50% lethal doses several logs lower than that in wild-type mice. This hypersusceptiblity was also associated with bacterial dissemination to the liver and spleen and increased lung permeability in Cy mice. Vaccination of the mice prior to treatment resulted in better survival and lower bacterial loads compared to vector-immunized mice. Although the treatments had no effect on antibody titers, this level of protection was still lower than that seen in untreated vaccinated mice. Administration of antibodies directly to the site of infection at the time of bacterial delivery prolonged survival and lowered bacterial loads in the immunocompromised mice. These results demonstrate the importance of white blood cells while still suggesting a critical role for antibodies in protection againstP. aeruginosainfection.