Protective immune responses to the 42-kilodalton (kDa) region of Plasmodium yoelii merozoite surface protein 1 are induced by the C-terminal 19-kDa region but not by the adjacent 33-kDa region
Protective immune responses to the 42-kilodalton (kDa) region of Plasmodium yoelii merozoite surface protein 1 are induced by the C-terminal 19-kDa region but not by the adjacent 33-kDa region
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DOI：
10.1128/iai.70.2.820-825.2002
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发表时间：
2002-02-01
影响因子：
3.1
通讯作者：
Riley, EM
中科院分区：
文献类型：
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作者：
Ahlborg, N;Ling, IT;Riley, EM
用约氏疟原虫裂殖子表面蛋白 1 (MSP1(42)) 的 42 kDa 区域或其 19 kDa C 末端加工产物 (MSP1(19)) 给小鼠接种疫苗可以在小鼠中引发保护性抗体反应。为了研究 MSP1(42) 的 33 kDa N 末端片段 (MSP1(33)) 是否也能诱导保护，将编码 MSP1(33) 的基因片段表达为谷胱甘肽 S-转移酶 (GST) 融合蛋白。 C57BL/6 和 BALB/c 小鼠用 GST-MSP1(33) 进行免疫，随后用致命的约氏疟原虫 YM 血期寄生虫进行攻击。 GST-MSP1(33) 未能诱导保护，并且所有小鼠均出现明显的寄生虫血症，其水平与幼稚或对照（GST 免疫）小鼠相似；如前所述，用 GST-MSP1(19) 免疫的小鼠受到保护。通过酶联免疫吸附测定和免疫荧光分析对 MSPI 的特异性攻击前免疫球蛋白 G (IgG) 抗体反应。尽管没有受到保护，但用 MSP1(33) 免疫的几只小鼠的抗体滴度（所有 IgG 亚类）与用 MSP1(19) 免疫后受到保护的小鼠的抗体滴度相当或更高。 P. yoelii MSP1(33) 引发强烈但非保护性抗体反应的发现可能对基于恶性疟原虫或间日疟原虫 MSP1(42) 的人类疫苗的设计具有影响。
Vaccination of mice with the 42-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP1(42)) or its 19-kDa C-terminal processing product (MSP1(19)) can elicit protective antibody responses in mice. To investigate if the 33-kDa N-terminal fragment (MSP1(33)) of MSP1(42) also induces protection, the gene segment encoding MSP1(33) was expressed as a glutathione S-transferase (GST) fusion protein. C57BL/6 and BALB/c mice were immunized with GST-MSP1(33) and subsequently challenged with the lethal P. yoelii YM blood stage parasite. GST-MSP1(33) failed to induce protection, and all mice developed patent parasitemia at a level similar to that in naive or control (GST-immunized) mice; mice immunized with GST-MSP1(19) were protected, as has been shown previously. Specific prechallenge immunoglobulin G (IgG) antibody responses to MSPI were analyzed by enzyme-linked immunosorbent assay and immunofluorescence. Despite being unprotected, several mice immunized with MSP1(33) had antibody titers (of all IgG subclasses) that were comparable to or higher than those in mice that were protected following immunization with MSP1(19). The finding that P. yoelii MSP1(33) elicits strong but nonprotective antibody responses may have implications for the design of vaccines for humans based on Plasmodium falciparum or Plasmodium vivax MSP1(42).