Unit of Infectious Disease, Microbiology, and Preventive Medicine, Hospitales Universitarios Virgen del Rocío, Edificio Laboratorio Anexo Caracola, Avenida Manuel Siurot s/n, 41013 Seville, Spain.
Infect Immun. 2011 Jan;79(1):518-26. doi: 10.1128/IAI.00741-10. Epub 2010 Oct 25.
Acinetobacter baumannii causes pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused by A. baumannii has increased dramatically over the last 30 years, while at the same time the treatment of these infections has been complicated by the emergence of antibiotic-resistant strains. Despite these trends, no vaccines or antibody-based therapies have been developed for the prevention of A. baumannii infection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane of A. baumannii was developed and tested in a murine sepsis model. Immunization elicited humoral and cellular responses that were able to reduce postinfection bacterial loads, reduce postinfection proinflammatory cytokine levels in serum, and protect mice from infection with human clinical isolates of A. baumannii. A single administration of the vaccine was able to elicit protective immunity in as few as 6 days postimmunization. In addition, vaccine antiserum was used successfully to therapeutically rescue naïve mice with established infection. These results indicate that prophylactic vaccination and antibody-based therapies based on an outer membrane complex vaccine may be viable approaches to preventing the morbidity and mortality caused by this pathogen.
鲍曼不动杆菌可引起肺炎、菌血症和皮肤软组织感染,主要发生在住院环境中。在过去 30 年中,由鲍曼不动杆菌引起的感染发病率急剧上升,与此同时,由于出现了抗生素耐药菌株,这些感染的治疗变得更加复杂。尽管存在这些趋势,但尚未开发出用于预防鲍曼不动杆菌感染的疫苗或基于抗体的疗法。在这项研究中,开发了一种由鲍曼不动杆菌细菌膜上的多种表面抗原组成的外膜复合物疫苗,并在小鼠败血症模型中进行了测试。免疫接种可引发体液和细胞反应,从而降低感染后细菌负荷,降低血清中感染后促炎细胞因子水平,并保护小鼠免受人类临床分离株鲍曼不动杆菌的感染。单次接种疫苗可在免疫后 6 天内产生保护免疫力。此外,疫苗抗血清成功用于治疗已建立感染的新生小鼠。这些结果表明,基于外膜复合物疫苗的预防性接种和基于抗体的疗法可能是预防这种病原体引起的发病率和死亡率的可行方法。