Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
PLoS One. 2011;6(7):e22525. doi: 10.1371/journal.pone.0022525. Epub 2011 Jul 28.
GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials.
METHODOLOGY/PRINCIPAL FINDINGS: Thirty children one to five years of age were randomized to receive three doses of either 30 µg or 100 µg of GMZ2, or rabies vaccine. GMZ2, adjuvanted in aluminum hydroxide, was administered on Days 0, 28 and 56. All participants received a full course of their respective vaccination and were followed up for one year. Both 30 µg and 100 µg GMZ2 vaccine doses were well tolerated and induced antibodies and memory B-cells against GMZ2 as well as its antigenic constituents MSP3 and GLURP. After three doses of vaccine, the geometric mean concentration of antibodies to GMZ2 was 19-fold (95%CI: 11,34) higher in the 30 µg GMZ2 group than in the rabies vaccine controls, and 16-fold (7,36) higher in the 100 µg GMZ2 group than the rabies group. Geometric mean concentration of antibodies to MSP3 was 2.7-fold (1.6,4.6) higher in the 30 µg group than in the rabies group and 3.8-fold (1.5,9.6) higher in the 100 µg group. Memory B-cells against GMZ2 developed in both GMZ2 vaccinated groups.
CONCLUSIONS/SIGNIFICANCE: Both 30 µg as well as 100 µg intramuscular GMZ2 are immunogenic, well tolerated, and safe in young, malaria-exposed Gabonese children. This result confirms previous findings in naïve and malaria-exposed adults and supports further clinical development of GMZ2.
ClinicalTrials.gov NCT00703066.
GMZ2 是恶性疟原虫裂殖子表面蛋白 3（MSP3）和谷氨酸丰富蛋白（GLURP）的融合蛋白，可介导针对寄生虫血期的免疫反应。两项先前的 I 期临床试验，一项在欧洲初免成人中进行，一项在接触过疟疾的加蓬成人中进行，表明 GMZ2 具有良好的耐受性和免疫原性。在这里，我们报告了 GMZ2 在 1 至 5 岁加蓬儿童中的安全性和免疫原性数据，这些儿童是未来疟疾疫苗疗效试验的目标人群。
方法/主要发现：30 名 1 至 5 岁的儿童随机接受 30µg 或 100µg GMZ2 或狂犬病疫苗的三种剂量，佐剂为氢氧化铝。GMZ2 在第 0、28 和 56 天给药。所有参与者均接受了各自疫苗的全程接种，并随访了一年。30µg 和 100µg GMZ2 疫苗剂量均耐受良好，并诱导了针对 GMZ2 及其抗原成分 MSP3 和 GLURP 的抗体和记忆 B 细胞。在接种三剂疫苗后，30µg GMZ2 组的 GMZ2 抗体几何平均浓度比狂犬病疫苗对照组高 19 倍（95%CI：11，34），100µg GMZ2 组比狂犬病组高 16 倍（7，36）。30µg 组抗 MSP3 的抗体几何平均浓度比狂犬病组高 2.7 倍（1.6，4.6），100µg 组高 3.8 倍（1.5，9.6）。两组 GMZ2 疫苗接种者均产生了 GMZ2 记忆 B 细胞。
结论/意义：30µg 和 100µg 肌内 GMZ2 在年轻、接触过疟疾的加蓬儿童中均具有免疫原性、良好的耐受性和安全性。这一结果证实了先前在初免和接触过疟疾的成年人中的发现，并支持 GMZ2 的进一步临床开发。
ClinicalTrials.gov NCT00703066。
