Teti G, Calapai M, Calogero G, Tomasello F, Mancuso G, Galli A, Riggio G
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
Hybridoma. 1992 Feb;11(1):13-22. doi: 10.1089/hyb.1992.11.13.
We have obtained 41 monoclonal antibodies directed against type III group B streptococci by immunizing Balb/c mice with formalin-killed bacteria. All of these antibodies reacted with purified type-specific carbohydrate by enzyme-linked immunosorbent assay and immunoprecipitation tests. The epitope recognized by all of these antibodies was associated with terminal sialic acid residues, as indicated by abrogation of immune reactions by treatment of the type-specific carbohydrate with neuraminidase. Two purified monoclonal antibodies (the IgM P9D8 and the IgG3 P4F12) were further characterized for their protective activity in a neonatal rat model of infection. P9D8 and P4F12 antibodies were significantly protective when administered in a dose of 0.5 and 2.5 mg/kg, respectively, at the same time as 3 x 10(5) colony forming units of type III streptococci. Protection was still observed when the antibodies were given up to 9 h after challenge. No protection was afforded against infections with type Ia/c and II streptococci. Similarly, both antibodies effectively opsonized type III, but not Ia, Ib or II bacteria, in an in vitro assay. These and similar, previously described, monoclonal antibodies may be useful, possibly after "humanization" by genetic engineering, for the therapy of neonatal group B streptococcal infections.
我们用福尔马林灭活的细菌免疫Balb/c小鼠,获得了41种针对B族链球菌III型的单克隆抗体。通过酶联免疫吸附测定和免疫沉淀试验,所有这些抗体都能与纯化的型特异性碳水化合物发生反应。用神经氨酸酶处理型特异性碳水化合物后免疫反应消失,这表明所有这些抗体识别的表位与末端唾液酸残基有关。进一步对两种纯化的单克隆抗体(IgM P9D8和IgG3 P4F12)在新生大鼠感染模型中的保护活性进行了表征。当与3×10⁵个III型链球菌菌落形成单位同时给药时,P9D8和P4F12抗体分别以0.5和2.5mg/kg的剂量给药具有显著的保护作用。在攻击后9小时内给予抗体仍可观察到保护作用。对Ia/c型和II型链球菌感染没有提供保护作用。同样,在体外试验中,这两种抗体都能有效地调理III型细菌,但不能调理Ia、Ib或II型细菌。这些以及之前描述的类似单克隆抗体,可能在通过基因工程进行“人源化”后,对治疗新生儿B族链球菌感染有用。