TRANSMISSION BLOCKADE OF PLASMODIUM-FALCIPARUM MALARIA BY ANTI-PFS230-SPECIFIC ANTIBODIES IS ISOTYPE DEPENDENT
TRANSMISSION BLOCKADE OF PLASMODIUM-FALCIPARUM MALARIA BY ANTI-PFS230-SPECIFIC ANTIBODIES IS ISOTYPE DEPENDENT
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DOI：
10.1128/iai.63.2.467-471.1995
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发表时间：
1995-02-01
影响因子：
3.1
通讯作者：
SAUERWEIN, R
中科院分区：
文献类型：
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作者：
ROEFFEN, W;GEERAEDTS, F;SAUERWEIN, R
通过使用亲本杂交瘤细胞。 63F2A2 系产生抗 Pfs230 的免疫球蛋白同种型 G1（IgG1；63F2A2.1）特异性抗体，我们尝试富集杂交瘤细胞系（分别为 63F2A2.2b 和 63F2A2.2a）的下游开关变体 IgG2b 和 IgG2a 单克隆抗体（MAb）的合成。在生物测定中，无论是否存在补体，亲本 IgG1 都不会减少恶性疟原虫的传播。在膜饲实验中，MAb 63F2A2.2b 和 63F2A2.2a 可有效降低恶性疟原虫寄生虫对冈比亚按蚊的感染性。 63F2A2.2b 开关变体实现了 91% 的传输减少，63F2A2.2a 开关变体实现了超过 99% 的传输减少，但仅在存在活性人类补体的情况下。随后，通过在活性补体存在下新形成的大配子或合子的快速裂解，在体外证实了 MAb 63F2A2.2b 或 63F2A2.2a 的传播减少作用。无论补体是否存在，MAb 63F2A2.1 都不裂解新形成的大配子或合子。
By use of the parental hybridoma cell. line 63F2A2 that produces specific antibodies of immunoglobulin isotype G1 (IgG1; 63F2A2.1) against Pfs230, we attempted to enrich for the synthesis of the downstream switch variant IgG2b and IgG2a monoclonal antibodies (MAbs) of the hybridoma cell line (63F2A2.2b and 63F2A2.2a; respectively). The parental IgG1 did not reduce the Plasmodium falciparum transmission in a bioassay irrespective of the presence of complement. MAbs 63F2A2.2b and 63F2A2.2a were effective in reducing the infectivity of P. falciparum parasites to Anopheles gambiae mosquitoes in membrane-feeding experiments. A transmission reduction of 91% was accomplished by the 63F2A2.2b switch variant, and a reduction of greater than 99% was accomplished by the 63F2A2.2a switch variant, but only in the presence of active human complement. Subsequently, the transmission-reducing effect of MAb 63F2A2.2b or 63F2A2.2a was confirmed in vitro by the rapid lysis of newly formed macrogametes or zygotes in the presence of active complement. MAb 63F2A2.1 did not lyse the newly formed macrogametes or zygotes irrespective of the presence of complement.