Oral vaccination of BALB/c mice with Salmonella enterica serovar typhimurium expressing Pseudomonas aeruginosa O antigen promotes increased survival in an acute fatal pneumonia model
Oral vaccination of BALB/c mice with Salmonella enterica serovar typhimurium expressing Pseudomonas aeruginosa O antigen promotes increased survival in an acute fatal pneumonia model
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DOI：
10.1128/iai.72.12.7012-7021.2004
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发表时间：
2004-12-01
影响因子：
3.1
通讯作者：
Goldberg, JB
中科院分区：
文献类型：
--
作者：
DiGiandomenico, A;Rao, J;Goldberg, JB
铜绿假单胞菌是医院获得性肺炎的主要原因。我们比较了口服和腹膜内（i. p.）用表达铜绿假单胞菌血清群O 110抗原的减毒肠道沙门氏菌血清型鼠伤寒沙门氏菌SL 3261接种BALB/c小鼠，以在急性致死性肺炎模型中保护免受铜绿假单胞菌感染。口服和腹腔注射疫苗引起O 11特异性血清免疫球蛋白G（IgG）抗体，但伊加仅在口服免疫后观察到。以6倍和12倍50%致死剂量的O 11菌株（9882-80）经口接种疫苗的小鼠的挑战显示，与磷酸盐缓冲盐水（PBS）和载体处理的对照组相比，接受疫苗的小鼠的存活率增加;异源菌株6294（血清群O 6）的存活率无差异。此外，在i. p.接种动物中未观察到对9882-80的显著保护。从免疫小鼠中采集的支气管肺泡灌洗液在口服免疫小鼠中含有O 11特异性伊加和IgG，但在腹腔接种小鼠中仅含有中等水平的IgG。为了关联保护，用来自经口免疫动物的合并血清进行调理吞噬测定。观察到5株O 11临床分离株的有效杀灭，而6294未观察到杀灭，表明重组SL 3261口服疫苗诱导O 11特异性反应。接下来，我们确定了口服疫苗接种动物清除肺部细菌的能力。铜绿假单胞菌攻毒后，经口接种动物中的活菌数量显著少于PBS和载体处理的对照动物。我们的研究结果表明，口服免疫重组SL 3261是有效的保护对肺炎引起的铜绿假单胞菌。
Pseudomonas aeruginosa is a leading cause of nosocomial pneumonia. We compared the efficacies of oral and intraperitoneal (i.p.) vaccinations of BALB/c mice with attenuated Salmonella enterica serovar Typhimurium SL3261 expressing P. aeruginosa serogroup O110 antigen to protect against P. aeruginosa infection in an acute fatal pneumonia model. Oral and i.p. vaccines elicited O11-specific serum immunoglobulin G (IgG) antibodies, but IgA was observed only after oral immunization. Challenge of orally vaccinated mice with an O11 strain (9882-80) at 6 and 12 times the 50% lethal dose showed increased survival in mice that received the vaccine compared to phosphate-buffered saline (PBS)- and vector-treated controls; no difference in survival was seen with a heterologous strain, 6294 (serogroup O6). In addition, significant protection against 9882-80 was not observed in i.p. vaccinated animals. Bronchoalveolar lavage fluid taken from immunized mice harbored O11-specific IgA and IgG in orally immunized mice but only modest levels of IgG in i.p. vaccinated mice. To correlate protection, opsonophagocytosis assays were performed with pooled sera from orally immunized animals. Efficient killing of five O11 clinical isolates was observed, while no killing was noted with 6294, indicating that the recombinant SL3261 oral vaccine induces an O11-specific reaction. We next determined the ability of orally vaccinated animals to clear bacteria from their lungs. Following P. aeruginosa challenge, the numbers of viable bacteria were significantly fewer in orally vaccinated animals than in PBS- and vector-treated controls. Our results suggest that oral immunization with recombinant SL3261 is efficacious in protection against pneumonia caused by P. aeruginosa.