Roeffen W, Geeraedts F, Eling W, Beckers P, Wizel B, Kumar N, Lensen T, Sauerwein R
Department of Medical Microbiology, University of Nijmegen, The Netherlands.
Infect Immun. 1995 Feb;63(2):467-71. doi: 10.1128/iai.63.2.467-471.1995.
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.
利用产生针对Pfs230的免疫球蛋白同种型G1（IgG1；63F2A2.1）特异性抗体的亲代杂交瘤细胞系63F2A2，我们试图富集杂交瘤细胞系（分别为63F2A2.2b和63F2A2.2a）下游转换变体IgG2b和IgG2a单克隆抗体（MAb）的合成。亲代IgG1在生物测定中无论是否存在补体都不会降低恶性疟原虫的传播。在膜饲实验中，单克隆抗体63F2A2.2b和63F2A2.2a可有效降低恶性疟原虫对冈比亚按蚊的感染性。63F2A2.2b转换变体实现了91%的传播降低率，63F2A2.2a转换变体实现了大于99%的降低率，但仅在存在活性人补体的情况下。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，在体外证实了单克隆抗体63F2A2.2b或63F2A2.2a的传播降低效果。无论是否存在补体，单克隆抗体63F2A2.1都不会裂解新形成的大配子或合子。
