Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naive adults at the Walter Reed Army Institute of Research
Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naive adults at the Walter Reed Army Institute of Research
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DOI：
10.1016/j.vaccine.2008.02.048
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发表时间：
2008-04-24
期刊：
影响因子：
5.5
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：在实验挑战和现场试验中，S/AS02RTS免疫持续保护一些接种者免受疟疾感染。针对恶性疟疾的一个简短的免疫程序可以与扩大的免疫计划相兼容，或与其他预防措施相结合，中断疟疾流行或保护突然前往流行区的个人。方法：我们在40名健康的初治疟疾的成年人身上进行了两种不同剂量的RTS，S/AS02的开放标签2a期试验。队列1(n=20)按0、1、3个月计划免疫，队列2(n=20)按0、7、28天计划免疫。三周后，38名疫苗接种者和12名未免疫的传染病控制人员接受了疟疾挑战。结果：两种方案都具有良好的安全性和耐受性。抗环子孢子蛋白(CSP)抗体峰值GMC在队列1(78 mU g/mL；95%CI：45~134)和队列2(65 mU g/mL；95%CI：40~104)中相似。队列1的疫苗效力为45%(95%可信区间：18-62%)，队列2的疫苗效力为39%(95%可信区间：11-56%)。受保护志愿者的抗CsP抗体GMC(114mU g/m L)高于志愿者(P=0.019)，原虫血症起病时间延迟2天(70 mU g/m L)或无延迟(30 m u g/m L)。在体外和培养的ELISPOT试验中，仅在队列1的受保护志愿者的PBMC中有更高的CSP特异性干扰素-γ应答的趋势，而在队列2中没有。结论：在初治疟疾的成年人中，三剂RTS、S/AS02方案在0、1和3个月的方案或缩短的0、7和28天方案上的疗效与先前报道的两种方案在0、7和28天给药的两次试验没有明显差异。1个月获得47%(95%CI：-19%至76%)的保护，另一项试验获得42%(95%CI：5-63%)的保护。观察到CSP特异性抗体与预防疟疾挑战有很强的关联，并证实了其他研究中的类似观察结果。随后在非洲儿童和婴儿中进行的辅助性RTS，S的0，1和2个月的试验证明了良好的安全性和有效性。爱思唯尔有限公司出版。
Background: Immunization with RTS,S/AS02 consistently protects some vaccinees against malaria infection in experimental challenges and in field trials. A brief immunization schedule against falciparum malaria would be compatible with the Expanded Programme on Immunization, or in combination with other prevention measures, interrupt epidemic malaria or protect individuals upon sudden travel to an endemic area.Methods: We conducted an open label, Phase 2a trial of two different full dose schedules of RTS,S/AS02 in 40 healthy malaria-naive adults. Cohort 1 (n=20) was immunized on a 0, 1, and 3 month schedule and Cohort 2 (n = 20) on a 0, 7, and 28 day schedule. Three weeks later, 38 vaccinees and 12 unimmunized infectivity controls underwent malaria challenge.Results: Both regimens had a good safety and tolerability profile. Peak GMCs of antibody to the circumsporozoite protein (CSP) were similar in Cohort 1 (78 mu g/mL; 95% CI: 45-134) and Cohort 2 (65 mu g/mL; 95% CI: 40-104). Vaccine efficacy for Cohort 1 was 45% (95% CI: 18-62%) and for Cohort 2, 39% (95% CI: 11-56%). Protected volunteers had a higher GMC of anti-CSP antibody (114 mu g/mL) than did volunteers with a 2-day delay (70 mu g/mL) or no delay (30 mu g/mL) in the time to onset of parasitemia (Kruskal-Wallis, p = 0.019). A trend was seen for higher CSP-specific IFN-gamma responses in PBMC from protected volunteers only in Cohort 1, but not in Cohort 2, for ex vivo and for cultured ELISPOT assays.Conclusion: In malaria-naive adults, the efficacy of three-dose RTS,S/AS02 regimens on either a 0, 1, and 3 month schedule or an abbreviated 0, 7, and 28 day schedule was not discernibly different from two previously reported trials of two-dose regimens given at 0, 1 month that conferred 47% (95% CI: - 19 to 76%) protection and in another trial 42% (95% CI: 5-63%). A strong association of CSP-specific antibody with protection against malaria challenge is observed and confirms similar observations made in other studies. Subsequent trials of adjuvanted RTS,S in African children and infants on a 0, 1, and 2 month schedule have demonstrated a favorable safety and efficacy profile. Published by Elsevier Ltd.