Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules

Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules
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DOI:
10.1016/s0264-410x(99)00530-7
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发表时间:
2000-03-06
期刊:
影响因子:
5.5
通讯作者:
Becker, RS
Becker, RS
中科院分区:
医学3区
文献类型:
--
作者:
Nabors, GS;Braun, PA;Becker, RS

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肺炎球菌表面蛋白 A (PspA) 是一种高度可变的蛋白质,存在于所有肺炎球菌菌株中。为了获得成功,基于 PspA 的肺炎链球菌疫苗必须诱导具有广泛交叉反应性的抗体。为了确定是否可以在人体中诱导交叉反应抗体,我们评估了用 Rx1 菌株的重组进化枝 2 PspA 免疫的成人血清。用5-125μg rPspA免疫导致循环抗PspA抗体以及与异源rPspA分子反应的抗体显着增加。与免疫前血清相比,免疫后血清与表达多种 PspA 和荚膜类型的 37 种肺炎球菌菌株的结合增加。人抗rPspA的跨进化枝反应性程度大致遵循与非进化枝2抗原的序列同源性的量。据推测,人类自然暴露于肺炎链球菌导致的抗体对 PspA 的交叉反应范围有所扩大。 (C) 2000 Elsevier Science Ltd. 保留所有权利。
Pneumococcal surface protein A (PspA) is a highly variable protein found on all strains of pneumococci. To be successful, a PspA-based vaccine for S. pneumoniae must induce antibodies that are broadly cross-reactive. To address whether cross-reactive antibodies could be induced in man, we evaluated serum from adults immunized with recombinant clade 2 PspA from strain Rx1. Immunization with 5-125 mu g rPspA lead to a significant increase in circulating anti-PspA antibodies, as well as antibodies reactive to heterologous rPspA molecules. Increased binding of post-immune sera to 37 pneumococcal strains expressing a variety of PspA and capsule types was observed, Versus pre-immune sera. The extent of cross-clade reactivity of human anti-rPspA followed roughly the amount of sequence homology to the non-clade 2 antigens. It is hypothesized that priming of humans by natural exposure to S. pneumoniae contributes to the breadth of the cross-reactivity of antibody to PspA. (C) 2000 Elsevier Science Ltd. All rights reserved.