Human antibodies specific for the high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae mediate opsonophagocytic activity.
Human antibodies specific for the high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae mediate opsonophagocytic activity.
复制标题
对不可分型流感嗜血杆菌高分子量粘附蛋白具有特异性的人类抗体介导调理吞噬活性。
DOI：
10.1128/iai.71.12.6884-6891.2003
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发表时间：
2003
影响因子：
3.1
通讯作者：
Barenkamp,StephenJ
中科院分区：
文献类型：
--
作者：
Winter,LindaE;Barenkamp,StephenJ
75%的流感嗜血杆菌表达HMW 1和HMW 2样粘附蛋白，针对这些蛋白的抗体在动物感染模型中具有保护作用。本研究的目的是在体外补体依赖性调理吞噬试验中确定对这些蛋白质具有特异性的人抗体的功能活性。人早幼粒细胞系HL-60作为吞噬细胞的来源，静脉注射免疫球蛋白（IVIG）的商业制剂作为人抗体的来源。从四个原型nontypeableH中纯化高分子量（HMW）蛋白。用于制备固相亲和柱。将IVIG吸附在各色谱柱上，以去除菌株特异性抗HMW抗体，并回收亲和纯化的抗HMW抗体组分。未吸附的IVIG以1：80至1：320的滴度杀死每种原型菌株。HMW-吸附的血清表现出四倍下降调理吞噬滴度对同源株相比，未吸附的IVIG。亲和纯化的抗HMW抗体制剂显示针对相应同源菌株的调理吞噬滴度为1：20至1：80，针对异源菌株的调理吞噬滴度高达1：80。亲和纯化的抗HMW抗体制备物均未对代表性的不可分型H具有调理吞噬作用。流感病毒株不表达HMW 1或HMW 2样蛋白。这些数据表明，人抗体特异性的HMW 1/HMW 2样粘附蛋白的nontypeableH。流感病毒是调理吞噬性的，并且这种抗体识别不相关的不可分型的H.流感病毒株这些结果为继续研究HMW 1/HMW 2样蛋白作为潜在的疫苗候选物用于预防由于不可分型H引起的疾病提供了依据。流感。
The HMW1- and HMW2-like adhesion proteins of nontypeableHaemophilus influenzaeare expressed by 75% of these strains, and antibodies directed against these proteins are protective in animal models of infection. The purpose of the present study was to define the functional activity of human antibodies specific for these proteins in an in vitro complement-dependent opsonophagocytic assay. Human promyelocytic cell line HL-60 served as the source of phagocytic cells, and a commercial preparation of intravenous immunoglobulin (IVIG) served as the source of human antibodies. High-molecular-weight (HMW) proteins were purified from four prototype nontypeableH. influenzaestrains and used to prepare solid-phase affinity columns. IVIG was adsorbed on each column to remove strain-specific anti-HMW antibodies and to allow recovery of affinity-purified anti-HMW antibody fractions. Unadsorbed IVIG killed each of the prototype strains at titers of 1:80 to 1:320. HMW-adsorbed sera demonstrated fourfold decreases in opsonophagocytic titer against the homologous strains compared to unadsorbed IVIG. Affinity-purified anti-HMW antibody preparations demonstrated opsonophagocytic titers of 1:20 to 1:80 against the respective homologous strains and opsonophagocytic titers as high as 1:80 against heterologous strains. None of the affinity-purified anti-HMW antibody preparations was opsonophagocytic for a representative nontypeableH. influenzaestrain that did not express HMW1- or HMW2-like proteins. These data demonstrate that human antibodies specific for the HMW1/HMW2-like adhesion proteins of nontypeableH. influenzaeare opsonophagocytic and that such antibodies recognize epitopes shared by the HMW proteins of unrelated nontypeableH. influenzaestrains. These results argue for continued investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for prevention of disease due to nontypeableH. influenzae.