Randomized, Double-Blind, Phase 2a Trial of Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria-Naive Adults: Safety, Efficacy, and Immunologic Associates of Protection
Randomized, Double-Blind, Phase 2a Trial of Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria-Naive Adults: Safety, Efficacy, and Immunologic Associates of Protection
复制标题
DOI：
10.1086/600120
复制
发表时间：
2009-08-01
影响因子：
6.4
通讯作者：
Heppner, D. Gray, Jr.
中科院分区：
文献类型：
--
作者：
Kester, Kent E.;Cummings, James F.;Heppner, D. Gray, Jr.
背景。为了进一步提高疟疾疫苗RTS，S/AS02A的功效，我们测试了使用AS01B佐剂系统（葛兰素史克生物制品）配制的RTS，S抗原。方法。在一项双盲随机试验中，102 名健康志愿者被平均分配，在研究的第 0、1 和 2 个月接受 RTS,S/AS01B 或 RTS,S/AS02A 疫苗，然后进行疟疾攻击。 5 个月后，受保护的疫苗接种者再次接受注射。结果。 RTS,S/AS01B 和 RTS,S/AS02A 耐受性良好且安全。 RTS,S/AS01B 和 RTS,S/AS02A 的疗效分别为 50%（95% 置信区间 [CI], 32.9%-67.1%）和 32%（95% CI, 17.6%-47.6%）。在初始攻击时，RTS、S/AS01B 组具有更强的环子孢子蛋白 (CSP) 特异性免疫反应，包括更高的免疫球蛋白 (Ig) G 滴度、表达 >= 2 个激活标记物（白介素-2、干扰素 [IFN]-gamma、肿瘤坏死因子-α 或 CD40L）的 CSP 特异性 CD4(+) T 细胞数量更多，以及更多的离体 IFN-gamma 酶联免疫反应。免疫斑点 (ELISPOT) 比 RTS,S/AS02A 组的免疫斑点 (ELISPOT) 多。受保护的疫苗接种者具有更高的 CSP 特异性 IgG 滴度（几何平均滴度，188 vs 73 mg/mL；P
Background. To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS, S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals).Methods. In a double-blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later.Results. RTS,S/AS01B and RTS,S/AS02A were well tolerated and were safe. The efficacy of RTS,S/AS01B and RTS,S/AS02A was 50% (95% confidence interval [CI], 32.9%-67.1%) and 32% (95% CI, 17.6%-47.6%), respectively. At the time of initial challenge, the RTS, S/AS01B group had greater circumsporozoite protein (CSP)-specific immune responses, including higher immunoglobulin (Ig) G titers, higher numbers of CSP-specific CD4(+) T cells expressing >= 2 activation markers (interleukin-2, interferon [IFN]-gamma, tumor necrosis factor-alpha, or CD40L), and more ex vivo IFN-gamma enzyme-linked immunospots (ELISPOTs) than did the RTS,S/AS02A group. Protected vaccine recipients had a higher CSP-specific IgG titer (geometric mean titer, 188 vs 73 mg/mL; P