Field S K, Morrison D C
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66160.
Infect Immun. 1994 Sep;62(9):3994-9. doi: 10.1128/iai.62.9.3994-3999.1994.
Recently, we described the generation and characterization of an Armenian hamster Ab2 beta anti-idiotype monoclonal antibody (MAb4G2) specific for the binding site of a mouse monoclonal antibody, MAbY1-4A6, directed against the conserved 2-keto-3-deoxyoctulosonate (Kdo)-containing inner-core region of lipopolysaccharide (LPS) (S. K. Field, M. Pollack, and D. C. Morrison, Microb. Pathog. 15:103-120, 1993). In that study, mice and hamster immunized with MAb4G2 generated serum immunoglobulin G and M (IgG and IgM) antibodies which cross-react with Salmonella minnesota R595-chemotype rough mutant LPS (Re-LPS). In this report, we demonstrate that in C3Heb/FeJ mice, MAb4G2 elicits an immune response which is characterized by specific binding of antibody to Re-LPS, as assessed by enzyme-linked immunosorbent assay. The practical use of MAb4G2 as a potentially effective therapeutic agent against gram-negative bacterial sepsis is suggested by the demonstration that immunization of these mice with MAb4G2 results in significant protection of D-galactosamine-sensitized animals against an otherwise lethal dose of Re-LPS. Assessment of the temporal changes in Re-LPS-specific serum antibody titers from mice immunized with MAb4G2 or Re-LPS over a 40-day period indicates that immunization with Re-LPS elicits significantly higher titers of serum IgM antibodies compared with those in animals immunized with MAb4G2. Conversely, two immunizations with MAb4G2 result in an up to 10-fold increase in anti-Re-LPS-specific IgG serum antibody titers relative to those obtained in mice immunized with Re-LPS. Nineteen days after the secondary boost with MAb4G2, anti-Re-LPS-specific IgG serum antibody titers were significantly higher (three- to fourfold) compared with those in Re-LPS-treated animals. Initial immunization with the anti-idiotype antibody primes animals for enhanced secondary responses to Re-LPS, as assessed by the titers of anti-Re-LPS-specific IgG profiles. These data suggest the potential utility of MAb4G2 as a candidate vaccine against the lethal properties of gram-negative bacterial LPS.
最近，我们描述了一种亚美尼亚仓鼠抗独特型单克隆抗体（MAb4G2）的产生和特性，该抗体特异性针对小鼠单克隆抗体MAbY1-4A6的结合位点，MAbY1-4A6针对脂多糖（LPS）保守的含2-酮-3-脱氧辛糖酸（Kdo）的内核区域（S.K.菲尔德、M.波拉克和D.C.莫里森，《微生物致病机制》15:103-120，1993年）。在该研究中，用MAb4G2免疫的小鼠和仓鼠产生了与明尼苏达沙门氏菌R595化学型粗糙突变体LPS（Re-LPS）发生交叉反应的血清免疫球蛋白G和M（IgG和IgM）抗体。在本报告中，我们证明，在C3Heb/FeJ小鼠中，MAb4G2引发的免疫反应的特征是抗体与Re-LPS特异性结合，这通过酶联免疫吸附测定法评估。通过用MAb4G2免疫这些小鼠可使D-半乳糖胺致敏的动物对否则会致死剂量的Re-LPS产生显著保护作用，这表明MAb4G2作为一种针对革兰氏阴性菌败血症的潜在有效治疗剂具有实际应用价值。对用MAb4G2或Re-LPS免疫的小鼠在40天内Re-LPS特异性血清抗体滴度的时间变化评估表明，与用MAb4G2免疫的动物相比，用Re-LPS免疫可引发显著更高滴度的血清IgM抗体。相反，与用Re-LPS免疫的小鼠相比，用MAb4G2进行两次免疫可使抗Re-LPS特异性IgG血清抗体滴度提高多达10倍。在用MAb4G2进行二次加强免疫19天后，抗Re-LPS特异性IgG血清抗体滴度与用Re-LPS处理的动物相比显著更高（三到四倍）。通过抗Re-LPS特异性IgG谱的滴度评估，用抗独特型抗体进行初次免疫可使动物对Re-LPS的二次反应增强。这些数据表明MAb4G2作为一种针对革兰氏阴性菌LPS致死特性的候选疫苗具有潜在效用。
