Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants
Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants
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DOI：
10.1056/nejmoa0807773
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发表时间：
2008-12-11
影响因子：
158.5
通讯作者：
Tanner, Marcel
中科院分区：
文献类型：
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作者：
Abdulla, Salim;Oberholzer, Rolf;Tanner, Marcel
背景：RTS,S/AS 疟疾疫苗正在开发中，以便通过世界卫生组织的扩大免疫计划 (EPI) 提供。我们评估了将 RTS,S/AS02D 纳入婴儿标准 EPI 时间表的可行性。方法：在这项涉及坦桑尼亚巴加莫约 340 名婴儿的 2B 期单中心、双盲对照试验中，我们随机分配 340 名婴儿于 8 点、12 点接受三剂 RTS,S/AS02D 疫苗或乙型肝炎疫苗。 16 周龄。所有婴儿还接种了含有白喉和破伤风类毒素的疫苗、全细胞百日咳疫苗和 B 型流感嗜血杆菌结合疫苗 (DTPw/Hib)。主要目标是在 9 个月的监测期内发生严重不良事件，并证明与乙型肝炎疫苗相比，同时接种 RTS、S/AS02D 疫苗对 EPI 疫苗（DTPw/Hib 和乙型肝炎表面抗原）的反应不劣势。次要目标是检测恶性疟原虫环子孢子抗体和对抗疟疾感染的功效。结果：在 170 名接受 RTS,S/AS02D 疫苗的婴儿中，有 31 名报告了至少一种严重不良事件（18.2%；95% 置信区间 [CI]，12.7 至 24.9），在 170 名接受乙型肝炎的婴儿中，有 42 名报告了至少一种严重不良事件。 疫苗（24.7%；95% CI，18.4 至 31.9）。结果表明，RTS,S/AS02D 疫苗在对 EPI 抗原的抗体反应方面不逊色。接种后 1 个月，接受 RTS,S/AS02D 疫苗的婴儿在酶联免疫吸附测定 (ELISA) 中显示抗环子孢子抗体血清滴度呈阳性。在第三剂疫苗后的 6 个月内，RTS,S/AS02D 疫苗对首次感染恶性疟原虫的有效性为 65.2%（95% CI，20.7 至 84.7；P=0.01）。 结论：在婴儿中使用 RTS,S/AS02D 疫苗具有良好的安全性，不会干扰 对共同施用的 EPI 抗原的免疫反应，并降低疟疾感染的发生率。 （ClinicalTrials.gov 编号，NCT00289185。）。
Background: The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants.Methods: In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives.Results: At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01).Conclusions: The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.).