Gozalo A, Lucas C, Cachay M, Wellde B T, Hall T, Bell B, Wood J, Watts D, Wooster M, Lyon J A, Moch J K, Haynes J D, Williams J S, Holland C, Watson E, Kester K E, Kaslow D C, Ballou W R
U.S. Naval Medical Research Institute Detachment, Lima, Peru.
Am J Trop Med Hyg. 1998 Dec;59(6):991-7. doi: 10.4269/ajtmh.1998.59.991.
Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.
用针对酵母表达的重组FVO或恶性疟原虫裂殖子表面蛋白-1(MSP-1)19k-D C末端片段(MSP-1(19))产生的纯化兔免疫球蛋白,输注到未感染过疟疾的南美白绢猴体内,这些猴子随后立即受到FVO无性期疟原虫的攻击。对照猴子接受针对有性期抗原Pfs25产生的兔免疫球蛋白,或从经恶性疟原虫感染和药物治愈免疫的猴子获得的南美白绢猴超免疫血清。兔抗MSP-1(19)的被动转移未能预防同源或异源攻击,与阴性对照相比,在潜伏期或治疗时间上没有差异。有趣的是,兔抗MSP-1(19),而不是抗Pfs25免疫球蛋白和免疫猴血清,阻止了受感染猴子产生针对MSP-1(19)片段的抗体,表明这些抗体在体内与天然MSP-1(19)抗原发生反应。接受南美白绢猴免疫血清的两只猴子的潜伏期和治疗时间大大延迟,这两只猴子都发展为慢性间歇性低水平感染。体外寄生虫生长抑制试验(GIA)证实,浓缩的抗MSP-1(19)免疫球蛋白(4.8mg/ml)存在抑制活性(最大抑制率为40%),但我们在体内达到的峰值浓度(1mg/ml)在体外没有抑制作用。通过被动转移获得的亚抑制水平的抗MSP-1(19)抗体对恶性疟原虫攻击没有保护作用。