Kester Kent E, Cummings James F, Ofori-Anyinam Opokua, Ockenhouse Christian F, Krzych Urszula, Moris Philippe, Schwenk Robert, Nielsen Robin A, Debebe Zufan, Pinelis Evgeny, Juompan Laure, Williams Jack, Dowler Megan, Stewart V Ann, Wirtz Robert A, Dubois Marie-Claude, Lievens Marc, Cohen Joe, Ballou W Ripley, Heppner D Gray
Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910, USA.
J Infect Dis. 2009 Aug 1;200(3):337-46. doi: 10.1086/600120.
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).
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.
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 mug/mL; P < .001), higher numbers of CSP-specific CD4(+) T cells per 10(6) CD4(+) T cells (median, 963 vs 308 CSP-specific CD4(+) T cells/10(6) CD4(+) T cells; P < .001), and higher numbers of ex vivo IFN-gamma ELISPOTs (mean, 212 vs 96 spots/million cells; P < .001). At rechallenge, 4 of 9 vaccine recipients in each group were still completely protected.
The RTS,S/AS01B malaria vaccine warrants comparative field trials with RTS,S/AS02A to determine the best formulation for the protection of children and infants. The association between complete protection and immune responses is a potential tool for further optimization of protection. Trial registration. ClinicalTrials.gov identifier NCT00075049.
为进一步提高疟疾疫苗RTS,S/AS02A的效力，我们测试了使用AS01B佐剂系统（葛兰素史克生物制品公司）配制的RTS,S抗原。
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，随后进行疟疾攻击。受到疫苗保护的接受者在5个月后再次接受攻击。
RTS,S/AS01B和RTS,S/AS02A耐受性良好且安全。RTS,S/AS01B和RTS,S/AS02A的效力分别为50%（95%置信区间[CI]，32.9%-67.1%）和32%（95%CI，17.6%-47.6%）。在初次攻击时，RTS,S/AS01B组的环子孢子蛋白（CSP）特异性免疫反应更强，包括更高的免疫球蛋白（Ig）G滴度、更多表达2种激活标志物（白细胞介素-2、干扰素[IFN]-γ、肿瘤坏死因子-α或CD40L）的CSP特异性CD4(+)T细胞，以及比RTS,S/AS02A组更多的体外IFN-γ酶联免疫斑点（ELISPOT）。受到疫苗保护的接受者具有更高的CSP特异性IgG滴度（几何平均滴度，188对73μg/mL；P<.001）、每10(6)个CD4(+)T细胞中更高数量的CSP特异性CD4(+)T细胞（中位数，963对308个CSP特异性CD4(+)T细胞/10(6)个CD4(+)T细胞；P<.001），以及更高数量的体外IFN-γ ELISPOT（平均，212对96个斑点/百万细胞；P<.001）。在再次攻击时，每组9名疫苗接受者中有4名仍受到完全保护。
RTS,S/AS01B疟疾疫苗值得与RTS,S/AS02A进行比较性现场试验，以确定保护儿童和婴儿的最佳配方。完全保护与免疫反应之间的关联是进一步优化保护的潜在工具。试验注册。ClinicalTrials.gov标识符NCT00075049。
