Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4998-5003. doi: 10.1073/pnas.1111413109. Epub 2012 Feb 13.
Despite the importance of Salmonella infections in human and animal health, the target antigens of Salmonella-specific immunity remain poorly defined. We have previously shown evidence for antibody-mediating protection against invasive Salmonellosis in mice and African children. To generate an overview of antibody targeting in systemic Salmonellosis, a Salmonella proteomic array containing over 2,700 proteins was constructed and probed with immune sera from Salmonella-infected mice and humans. Analysis of multiple inbred mouse strains identified 117 antigens recognized by systemic antibody responses in murine Salmonellosis. Importantly, many of these antigens were independently identified as target antigens using sera from Malawian children with Salmonella bacteremia, validating the study of the murine model. Furthermore, vaccination with SseB, the most prominent antigenic target in Malawian children, provided mice with significant protection against Salmonella infection. Together, these data uncover an overlapping immune signature of disseminated Salmonellosis in mice and humans and provide a foundation for the generation of a protective subunit vaccine.
尽管沙门氏菌感染对人类和动物健康很重要,但沙门氏菌特异性免疫的靶抗原仍未明确定义。我们之前已经证明了针对侵袭性沙门氏菌病的抗体介导的保护作用在小鼠和非洲儿童中存在。为了全面了解系统性沙门氏菌病中的抗体靶向性,构建了一个包含超过 2700 种蛋白质的沙门氏菌蛋白质组阵列,并使用感染沙门氏菌的小鼠和人类的免疫血清进行了探测。对多个近交系小鼠品系的分析确定了 117 种抗原,这些抗原在系统性鼠伤寒沙门氏菌病中被系统性抗体反应识别。重要的是,使用来自马拉维患有沙门氏菌菌血症的儿童的血清,独立鉴定出许多这些抗原作为靶抗原,验证了该小鼠模型的研究。此外,用 SseB 进行疫苗接种,这是马拉维儿童中最突出的抗原性靶标,为小鼠提供了对沙门氏菌感染的显著保护。这些数据共同揭示了小鼠和人类弥散性沙门氏菌病的重叠免疫特征,并为保护性亚单位疫苗的生成奠定了基础。