Carvalho Leonardo J M, Alves Francisco A, Bianco Cesare, Oliveira Salma G, Zanini Graziela M, Soe Soe, Druilhe Pierre, Theisen Michael, Muniz José A P C, Daniel-Ribeiro Cláudio T
Laboratory of Malaria Research, Department of Immunology, Instituto Oswaldo Cruz/Fiocruz, Pavilhão Leonidas Deane, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ-Brazil 21045-900.
Clin Diagn Lab Immunol. 2005 Feb;12(2):242-8. doi: 10.1128/CDLI.12.2.242-248.2005.
The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end of the glutamate-rich protein (GLURP) and the C-terminal portion of the merozoite surface protein 3 (MSP3) of Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. The GLURP/MSP3 hybrid protein, expressed in Lactococcus lactis, was administered in association with alum, Montanide ISA720, or complete or incomplete Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (enzyme-linked immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge infection with P. falciparum FUP strain, all five monkeys from the GLURP/MSP3-alum group showed a rapid increase in parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-Montanide ISA720 had a delay in the course of parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group, parasitemia remained below this threshold in four of the five animals and, after it reached a peak, parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge infection boosted the antibody titers, and the importance of this event for vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against malaria infection if antibodies are induced at properly high titers.
在松鼠猴中评估了一种源自恶性疟原虫富含谷氨酸蛋白（GLURP）N末端和裂殖子表面蛋白3（MSP3）C末端部分的杂交重组蛋白的免疫原性和效力。在乳酸乳球菌中表达的GLURP/MSP3杂交蛋白与明矾、Montanide ISA720或完全或不完全弗氏佐剂（CFA/IFA）联合给药，每组五只动物。这三种制剂均显示具有免疫原性，但与其他两种制剂相比，明矾制剂的免疫原性较弱，尤其是CFA/IFA，其产生的抗体滴度非常高（酶联免疫吸附测定滴度>3,000,000，免疫荧光抗体试验滴度为6,400）。在用恶性疟原虫FUP株进行攻击感染后，GLURP/MSP3-明矾组的所有五只猴子的疟原虫血症迅速增加，达到10%并早期接受治疗。GLURP/MSP3-Montanide ISA720组中抗体滴度最高的两只猴子疟原虫血症病程延迟，由于血细胞比容低而延迟治疗。在GLURP/MSP3-CFA/IFA组中，五只动物中有四只的疟原虫血症保持在该阈值以下，在达到峰值后，疟原虫血症开始下降，猴子延迟治疗。当根据结果对所有动物进行分组时，观察到高抗体滴度与部分保护之间存在统计学上的显著关联。攻击感染提高了抗体滴度，并讨论了这一事件对该寄生虫流行地区疫苗效力的重要性。总之，这些数据表明，如果能诱导出足够高滴度的抗体，GLURP和MSP3可诱导针对疟疾感染的保护作用。
