Feng Hui-Min, Whitworth Ted, Olano Juan P, Popov Vsevolod L, Walker David H
Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Infect Immun. 2004 Apr;72(4):2222-8. doi: 10.1128/IAI.72.4.2222-2228.2004.
An emphasis on cellular immunity against Rickettsia has led to neglect of analysis of the role of antibody. The availability of an excellent mouse model of spotted fever rickettsiosis enabled investigation of a potential role of antibody in immunity to Rickettsia conorii. C3H severe combined immunodeficiency (SCID) mice were passively transfused with monoclonal antibodies against rickettsial outer membrane protein A (OmpA), OmpB, or lipopolysaccharide (LPS), polyclonal anti-R. conorii serum, Fab fragments of polyclonal antiserum, or no antibodies and then challenged 48 h later with 10 50% lethal doses (LD(50)) of R. conorii. All mice that received monoclonal antibodies against OmpA and two of four mice that received monoclonal antibodies against OmpB or polyclonal antisera were completely protected, but the recipients of anti-LPS antibodies or the Fab fragments were not protected. Polyclonal antibody treatment of C3H SCID mice that had been infected with 10 LD(50) of R. conorii 4 or 5 days earlier prolonged the life of the infected mice from 10.4 to 22.5 days and resulted in decreased levels of infectious rickettsiae in the spleen and liver 24 and 48 h later. Treatment with protective antibodies resulted in the development of large aggregates of R. conorii antigens in splenic macrophages and intraphagolysosomal rickettsial death and digestion. The kinetics of development of antibodies to R. conorii determined by immunoblotting revealed antibodies to LPS on day 6 and antibodies to OmpA and OmpB on day 12, when recovery from the infection had already occurred. Antibodies to particular epitopes of OmpA and OmpB may protect against reinfection, but they may not play a key role in immunity against primary infection. Antibodies might be useful for treating infections with antibiotic-resistant organisms, and some B-cell epitopes should be included in a subunit vaccine.
对立克次体细胞免疫的重视导致对抗体作用分析的忽视。斑点热立克次体病优秀小鼠模型的可得性使得能够研究抗体在抗康氏立克次体免疫中的潜在作用。将针对立克次体外膜蛋白A（OmpA）、OmpB或脂多糖（LPS）的单克隆抗体、多克隆抗康氏立克次体血清、多克隆抗血清的Fab片段或不给予抗体被动输注到C3H严重联合免疫缺陷（SCID）小鼠体内，48小时后用10个50%致死剂量（LD50）的康氏立克次体进行攻击。所有接受抗OmpA单克隆抗体的小鼠以及接受抗OmpB单克隆抗体或多克隆抗血清中的四只小鼠中的两只得到了完全保护，但接受抗LPS抗体或Fab片段的小鼠未得到保护。对4或5天前感染了10个LD50康氏立克次体的C3H SCID小鼠进行多克隆抗体治疗，可使感染小鼠的存活时间从10.4天延长至22.5天，并在24和48小时后导致脾脏和肝脏中感染性立克次体水平降低。用保护性抗体治疗导致脾脏巨噬细胞中形成大量康氏立克次体抗原聚集体以及吞噬溶酶体内立克次体死亡和消化。通过免疫印迹法测定的抗康氏立克次体抗体产生动力学显示，在感染已恢复的第6天出现抗LPS抗体，在第12天出现抗OmpA和OmpB抗体。针对OmpA和OmpB特定表位的抗体可能预防再次感染，但它们在抗初次感染免疫中可能不发挥关键作用。抗体可能有助于治疗对抗生素耐药生物体的感染，并且一些B细胞表位应包含在亚单位疫苗中。
