Scarff Jennifer M, Goldberg Joanna B
Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia, USA.
Clin Vaccine Immunol. 2008 Feb;15(2):367-75. doi: 10.1128/CVI.00419-07. Epub 2007 Dec 19.
Immunocompromised patients are highly susceptible to infection with Pseudomonas aeruginosa. Our laboratory previously showed that intranasal administration of an attenuated Salmonella strain expressing the P. aeruginosa lipopolysaccharide 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 to P. aeruginosa pneumonia 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 against P. aeruginosa infection.
免疫功能低下的患者极易感染铜绿假单胞菌。我们实验室先前表明，鼻内给予表达铜绿假单胞菌脂多糖O抗原的减毒沙门氏菌菌株，在鼻内攻击后对清除野生型小鼠体内的细菌和预防死亡有效。我们有兴趣研究这种疫苗策略在免疫功能低下小鼠中的疗效。分别通过腹腔注射环磷酰胺（Cy）或RB6-8C5抗体使小鼠出现白细胞减少或中性粒细胞减少，这些小鼠比未处理的小鼠更易患铜绿假单胞菌肺炎，其半数致死剂量比野生型小鼠低几个对数。这种高度易感性还与细菌扩散至肝脏和脾脏以及Cy小鼠肺通透性增加有关。与载体免疫的小鼠相比，在治疗前对小鼠进行疫苗接种可提高生存率并降低细菌载量。尽管这些处理对抗体滴度没有影响，但这种保护水平仍低于未处理的接种疫苗小鼠。在细菌接种时将抗体直接注射到感染部位可延长免疫功能低下小鼠的生存期并降低细菌载量。这些结果证明了白细胞的重要性，同时仍表明抗体在抵抗铜绿假单胞菌感染中起关键作用。
