Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a Target of Protective Antibodies
Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a Target of Protective Antibodies
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DOI：
10.1093/infdis/jiv154
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发表时间：
2015-10-01
影响因子：
6.4
通讯作者：
Zavala, Fidel
中科院分区：
文献类型：
--
作者：
Espinosa, Diego A.;Gutierrez, Gabriel M.;Zavala, Fidel
对动物和人类志愿者的研究表明，针对疟原虫环子孢子蛋白 (CSP) 重复区域的抗体可消除子孢子感染。然而，认识到重复序列侧翼的 N 和 C 末端区域在寄生虫感染性中发挥重要作用，提高了保护性抗体靶向它们的可能性。我们对恶性疟原虫 CSP N 末端具有特异性的单克隆抗体 (mAb5D5) 进行了鉴定，该抗体可抑制 CSP 的蛋白水解裂解，这是寄生虫感染肝细胞的关键要求。 mAb5D5 的过继转移强烈抑制表达恶性疟原虫 CSP N 末端的子孢子的体内感染，并且当与抗重复抗体结合时，这种保护作用大大增强。我们的结果表明，干扰寄生虫感染所需的分子过程的抗体可以发挥强大的体内保护活性，并表明针对疟原虫的红细胞前疫苗应包含 CSP N 末端区域。
Studies in animals and human volunteers demonstrate that antibodies against the repeat-region of the Plasmodium circumsporozoite protein (CSP) abrogate sporozoite infection. However, the realization that the N- and C-terminal regions flanking the repeats play essential roles in parasite infectivity raised the possibility that they could be targeted by protective antibodies. We characterized a monoclonal antibody (mAb5D5) specific for the N- terminus of the P. falciparum CSP, which inhibits the proteolytic cleavage of the CSP, a key requirement for parasite infection of hepatocytes. Adoptive transfer of mAb5D5 strongly inhibits the in vivo infection of sporozoites expressing the N- terminus of P. falciparum CSP, and this protection is greatly enhanced when combined with antirepeat antibodies. Our results show that antibodies interfering with molecular processes required for parasite infectivity can exert a strong in vivo protective activity and indicate that pre-erythrocytic vaccines against Plasmodium should include the CSP N- terminal region.