International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Sci Rep. 2018 Jul 12;8(1):10511. doi: 10.1038/s41598-018-28757-4.
Plasmodium vivax merozoite invasion is restricted to Duffy positive reticulocytes. Merozoite interaction with the Duffy antigen is mediated by the P. vivax Duffy binding protein (PvDBP). The receptor-binding domain of PvDBP maps to an N-terminal cysteine-rich region referred to as region II (PvDBPII). In addition, a family of P. vivax reticulocyte binding proteins (PvRBPs) mediates interactions with reticulocyte receptors. The receptor binding domain of P. vivax reticulocyte binding protein 1a (PvRBP1a) maps to a 30 kD region (PvRBP1a). Antibodies raised against recombinant PvRBP1a and PvDBPII recognize the native P. vivax antigens and inhibit their binding to host receptors. Rabbit IgG purified from sera raised against PvRBP1a and PvDBPII were tested individually and in combination for inhibition of reticulocyte invasion by P. vivax field isolates. While anti-PvDBPII rabbit IgG inhibits invasion, anti-PvRBP1a rabbit IgG does not show significant invasion inhibitory activity. Combining antibodies against PvDBPII and PvRBP1a also does not increase invasion inhibitory activity. These studies suggest that although PvRBP1a mediates reticulocyte invasion by P. vivax merozoites, it may not be useful to include PvRBP1a in a blood stage vaccine for P. vivax malaria. In contrast, these studies validate PvDBPII as a promising blood stage vaccine candidate for P. vivax malaria.
恶性疟原虫裂殖子入侵仅限于 Duffy 阳性网织红细胞。裂殖子与 Duffy 抗原的相互作用是由恶性疟原虫 Duffy 结合蛋白（PvDBP）介导的。PvDBP 的受体结合域映射到一个称为 II 区（PvDBPII）的 N 端富含半胱氨酸的区域。此外，恶性疟原虫网织红细胞结合蛋白（PvRBPs）家族介导与网织红细胞受体的相互作用。恶性疟原虫网织红细胞结合蛋白 1a（PvRBP1a）的受体结合域映射到一个 30kD 的区域（PvRBP1a）。针对重组 PvRBP1a 和 PvDBPII 产生的抗体识别天然的恶性疟原虫抗原，并抑制它们与宿主受体的结合。针对 PvRBP1a 和 PvDBPII 产生的兔 IgG 从血清中纯化，分别和联合用于抑制恶性疟原虫野外分离株对网织红细胞的入侵。虽然抗 PvDBPII 兔 IgG 抑制入侵，但抗 PvRBP1a 兔 IgG 不显示显著的入侵抑制活性。将针对 PvDBPII 和 PvRBP1a 的抗体联合使用也不会增加入侵抑制活性。这些研究表明，尽管 PvRBP1a 介导恶性疟原虫裂殖子对网织红细胞的入侵，但它可能不适用于恶性疟原虫疟疾的血期疫苗。相比之下，这些研究验证了 PvDBPII 作为恶性疟原虫疟疾血期疫苗候选物的前景。
