Passive Immunization with Antibodies against Three Distinct Epitopes on Plasmodium yoelii Merozoite Surface Protein 1 Suppresses Parasitemia
Passive Immunization with Antibodies against Three Distinct Epitopes on Plasmodium yoelii Merozoite Surface Protein 1 Suppresses Parasitemia
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DOI：
10.1128/iai.66.8.3925-3930.1998
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发表时间：
1998-08
影响因子：
3.1
通讯作者：
L. M. Spencer Valero;S. Ogun;S. Fleck;I. Ling;T. Scott-Finnigan;M. Blackman;A. Holder
中科院分区：
文献类型：
--
作者：
L. M. Spencer Valero;S. Ogun;S. Fleck;I. Ling;T. Scott-Finnigan;M. Blackman;A. Holder
摘要 我们已经生产了针对约氏疟原虫裂殖子表面蛋白 1 (MSP-1) 的单克隆抗体，并评估了它们通过被动免疫抑制血期寄生虫血症的能力。详细表征了六种免疫球蛋白 G 抗体：三种（B6、D3 和 F5）可有效抑制致死性血液阶段攻击感染，两种（B10 和 G3）部分有效，一种（B4）无效。 MSP-1 是裂殖子表面多肽复合物的前体；所有抗体均与该前体以及源自 MSP-1 C 末端的~42-kDa 片段 (MSP-142) 结合。 MSP-142 进一步裂解为由两个表皮生长因子 (EGF) 样模块组成的 N 端~33-kDa 多肽 (MSP-133) 和 C 端~19-kDa 多肽 (MSP-119)。 D3 与 MSP-142 反应，但不与 MSP-133 和 MSP-119 成分反应，B4 识别 MSP-133 N 末端内的表位，B6、B10、F5 和 G3 与 MSP-119 结合。 B10 和 G3 与需要两个 C 端 EGF 样模块才能形成的表位结合，而 B6 和 F5 与第一个 EGF 样模块中的表位结合。这些结果表明，约氏疟原虫MSP-1上的至少三个不同表位被抑制体内寄生虫血症的抗体所识别。
ABSTRACT We have produced monoclonal antibodies against Plasmodium yoelii merozoite surface protein 1 (MSP-1) and have assessed their ability to suppress blood stage parasitemia by passive immunization. Six immunoglobulin G antibodies were characterized in detail: three (B6, D3, and F5) were effective in suppressing a lethal blood stage challenge infection, two (B10 and G3) were partially effective, and one (B4) was ineffective. MSP-1 is the precursor to a complex of polypeptides on the merozoite surface; all of the antibodies bound to this precursor and to an ∼42-kDa fragment (MSP-142) that is derived from the C terminus of MSP-1. MSP-142 is further cleaved to an N-terminal ∼33-kDa polypeptide (MSP-133) and a C-terminal ∼19-kDa polypeptide (MSP-119) comprised of two epidermal growth factor (EGF)-like modules. D3 reacted with MSP-142 but not with either of the constituents MSP-133 and MSP-119, B4 recognized an epitope within the N terminus of MSP-133, and B6, B10, F5, and G3 bound to MSP-119. B10 and G3 bound to epitopes that required both C-terminal EGF-like modules for their formation, whereas B6 and F5 bound to epitopes in the first EGF-like module. These results indicate that at least three distinct epitopes on P. yoelii MSP-1 are recognized by antibodies that suppress parasitemia in vivo.