Yang C, Collins W E, Sullivan J S, Kaslow D C, Xiao L, Lal A A
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, Georgia 30341, USA.
Infect Immun. 1999 Jan;67(1):342-9. doi: 10.1128/IAI.67.1.342-349.1999.
Merozoite surface protein 1 is a candidate for blood-stage vaccines against malaria parasites. We report here an immunization study of Saimiri monkeys with a yeast-expressed recombinant protein containing the C terminus of Plasmodium vivax merozoite surface protein 1 and two T-helper epitopes of tetanus toxin (yP2P30Pv20019), formulated in aluminum hydroxide (alum) and block copolymer P1005. Monkeys immunized three times with yP2P30Pv20019 in block copolymer P1005 had significantly higher prechallenge titers of immunoglobulin G (IgG) antibodies against the immunogen and asexual blood-stage parasites than those immunized with yP2P30Pv20019 in alum, antigen alone, or phosphate-buffered saline (PBS) (P < 0.05). Their peripheral blood mononuclear cell proliferative responses to immunogen stimulation 4 weeks after the second immunization were also significantly higher than those from the PBS control group (P < 0.05). Upon challenge with 100,000 asexual blood-stage parasites 5 weeks after the last immunization, monkeys immunized with yP2P30Pv20019 in block copolymer P1005 had prepatent periods longer than those for the control alone group (P > 0.05). Three of the five animals in this group also had low parasitemia (peak parasitemia, </=20 parasites/microliter of blood). Partially protected monkeys had significantly higher levels of prechallenge antibodies against the immunogen than those unprotected (P < 0.05). There was also a positive correlation between the prepatent period and titers of IgG antibodies against the immunogen and asexual blood-stage parasites and a negative correlation between accumulated parasitemia and titers of IgG antibodies against the immunogen (P < 0.05). These results indicate that when combined with block copolymer and potent T-helper epitopes, the yeast-expressed P2P30Pv20019 recombinant protein may offer some protection against malaria.
裂殖子表面蛋白1是疟疾寄生虫血期疫苗的候选物。我们在此报告一项对松鼠猴的免疫研究,该研究使用了一种酵母表达的重组蛋白,其包含间日疟原虫裂殖子表面蛋白1的C末端和破伤风毒素的两个T辅助表位(yP2P30Pv20019),该重组蛋白用氢氧化铝(明矾)和嵌段共聚物P1005配制。用嵌段共聚物P1005中的yP2P30Pv20019免疫三次的猴子,与用明矾中的yP2P30Pv20019、单独抗原或磷酸盐缓冲盐水(PBS)免疫的猴子相比,针对免疫原和无性血期寄生虫的攻击前免疫球蛋白G(IgG)抗体滴度显著更高(P < 0.05)。第二次免疫后4周,它们对外周血单核细胞对免疫原刺激的增殖反应也显著高于PBS对照组(P < 0.05)。在最后一次免疫后5周用100,000个无性血期寄生虫攻击后,用嵌段共聚物P1005中的yP2P30Pv20019免疫的猴子的潜隐期比单独对照组的更长(P > 0.05)。该组五只动物中有三只也有低寄生虫血症(峰值寄生虫血症,≤20个寄生虫/微升血液)。部分受到保护的猴子针对免疫原的攻击前抗体水平显著高于未受保护的猴子(P < 0.05)。潜隐期与针对免疫原和无性血期寄生虫的IgG抗体滴度之间也存在正相关,累积寄生虫血症与针对免疫原的IgG抗体滴度之间存在负相关(P < 0.05)。这些结果表明,当与嵌段共聚物和有效的T辅助表位结合时,酵母表达的P2P30Pv20019重组蛋白可能对疟疾提供一定的保护。