Harris Shannon L, Tsao How, Ashton Lindsey, Goldblatt David, Fernsten Philip
Wyeth Vaccines Research, Pearl River, NY 10965, USA.
Clin Vaccine Immunol. 2007 Apr;14(4):397-403. doi: 10.1128/CVI.00241-06. Epub 2007 Feb 7.
Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (K(D)s) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) K(D) was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM K(D), 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the K(D), reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions.
抗体亲和力是抗体与其抗原之间多价相互作用的强度,是保护性免疫反应的一个重要特征。我们开发了一种抑制酶联免疫吸附测定法(ELISA)来测量针对C群脑膜炎奈瑟菌(MnC)荚膜多糖(PS)的抗体亲和力,并测定了100名接种MnC PS结合疫苗儿童血清的亲和力常数(K(D))。将这些亲和力常数与使用离液剂ELISA方案为相同血清获得的亲和力指数(AI)进行比较。初次免疫系列后,几何平均(GM)K(D)为674 nM,在免疫后的几个月内没有变化。然而,加强剂量后GM亲和力确实增加了(加强免疫后1个月GM K(D)为414 nM)。相比之下,GM AI从初次免疫系列后的初始值118增加到初次免疫系列完成后6个月的147,然后在加强免疫后进一步增加到178。在个体受试者水平上,亲和力常数和AI在初次免疫系列后和加强免疫后相关,但在加强免疫前不相关。这项工作表明,与K(D)相比,通过离液剂ELISA测量的AI反映了使抗体群体更不易被离液剂破坏的变化,而不会直接影响结合相互作用的强度。