Schreiber J R, Pier G B, Grout M, Nixon K, Patawaran M
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
J Infect Dis. 1991 Sep;164(3):507-14. doi: 10.1093/infdis/164.3.507.
Mucoid strains of Pseudomonas aeruginosa are the major pulmonary pathogens for cystic fibrosis patients. Opsonizing antibodies to the mucoid exopolysaccharide (MEP) antigen may protect animals and some cystic fibrosis patients from infection. However, MEP does not readily elicit opsonic antibodies either during chronic infection or after vaccination. To evaluate alternative means to induce opsonic antibodies, a murine monoclonal anti-idiotypic antibody directed to an opsonic monoclonal antibody specific to MEP was produced. The anti-idiotypic antibody bound to F(ab')2 fragments of the opsonic antibody, blocked binding to MEP, bound to cross-reactive idiotopes on human opsonic antibodies to MEP, and elicited MEP-specific antibodies in syngeneic and allogeneic mice. These anti-idiotype-induced, MEP-specific antibodies fixed complement to mucoid P. aeruginosa cells and opsonized them for phagocytic killing by human leukocytes. These studies demonstrate the potential utility of anti-idiotypic monoclonal antibody for generating protective immunity against bacterial polysaccharides.
铜绿假单胞菌的黏液样菌株是囊性纤维化患者的主要肺部病原体。针对黏液样胞外多糖(MEP)抗原的调理素抗体可能会保护动物和一些囊性纤维化患者免受感染。然而,无论是在慢性感染期间还是接种疫苗后,MEP都不容易引发调理素抗体。为了评估诱导调理素抗体的其他方法,制备了一种针对MEP特异性调理素单克隆抗体的鼠单克隆抗独特型抗体。该抗独特型抗体与调理素抗体的F(ab')2片段结合,阻断其与MEP的结合,与人类针对MEP的调理素抗体上的交叉反应独特型表位结合,并在同基因和异基因小鼠中引发MEP特异性抗体。这些抗独特型诱导的MEP特异性抗体将补体固定到黏液样铜绿假单胞菌细胞上,并使其被人白细胞吞噬杀伤。这些研究证明了抗独特型单克隆抗体在产生针对细菌多糖的保护性免疫方面的潜在效用。