Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya
Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya
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DOI：
10.1086/501459
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发表时间：
2006-04-15
影响因子：
11.8
通讯作者：
Marsh, K
中科院分区：
文献类型：
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作者：
Bejon, P;Peshu, N;Marsh, K
背景。我们正在开发一种针对疟疾的异源初免-加强疫苗策略。这种方法使用不同载体进行顺序免疫来传递常见的红细胞前疟疾抗原。先前在疟疾非流行地区的研究中已记录了有效性和安全性的初步证据。在进行更大规模的研究以确定该疫苗策略在该领域的有效性之前，现在需要来自疟疾流行地区的额外安全数据。其他改良安卡拉痘苗病毒 (MVA) 重组体和初免加强免疫正在开发中，作为针对人类免疫缺陷病毒 (HIV) 感染、结核病和癌症的疫苗，MVA 是一种候选减毒天花疫苗。肯尼亚的 73 名成人（其中 7 名艾滋病毒呈阳性）和 22 名儿童皮内接种了疟疾候选疫苗。这些疫苗使用减毒鸡痘株 FP9 和 2 种红细胞前疟疾抗原、与红细胞前阶段抗原 TRAP (ME-TRAP) 和环子孢子蛋白 (CS) 结合的多个红细胞前阶段表位中的任一种的 MVA 重组体。记录不良事件。结果。反应原性轻微。如果在 FP9 引发后给予 MVA，则引起的皮肤反应频率和严重程度都会降低。半剂量降低了全身反应原性的频率和严重程度，并且特定的疫苗批次与不同的反应原性相关。出乎意料的是，之前对 ME-TRAP 抗原的免疫似乎可以防止免疫后的局部反应。结论。如果最终目的是在 FP9 引发后使用 MVA，则之前单独对 MVA 进行的测试会高估反应原性。这些重组载体似乎是安全的，适合用于非洲儿童和艾滋病毒阳性个体的大规模研究。
Background. We are developing a heterologous prime-boost vaccine strategy against malaria. This approach uses sequential immunization with different vectors to deliver a common preerythrocytic malaria antigen. Preliminary evidence of efficacy and safety has been previously documented in studies from an area where malaria is nonendemic. Additional safety data from an area where malaria is endemic are now required before larger-scale studies are undertaken to determine the efficacy of this vaccine strategy in the field. Other modified vaccinia virus Ankara (MVA) recombinants and prime-boost immunizations are being developed as vaccines against human immunodeficiency virus (HIV) infection, tuberculosis, and cancer, and MVA is a candidate attenuated smallpox vaccine.Methods. Candidate vaccines against malaria were intradermally administered to 73 adults ( 7 of whom were HIV positive) and 22 children in Kenya. These vaccines used the attenuated fowlpox strain FP9 and the MVA recombinant for either of 2 preerythrocytic malaria antigens, multiple preerythrocytic-stage epitopes joined with the preerythrocytic-stage antigen TRAP (ME-TRAP) and the circumsporozoite protein ( CS). Adverse events were recorded.Results. Reactogenicity was mild. MVA caused less frequent and less severe cutaneous reaction if given after FP9 priming. Half doses reduced the frequency and the severity of systemic reactogenicity, and particular vaccine lots were associated with different reactogenicities. Unexpectedly, prior immunity to the ME-TRAP antigen appeared to be protective against local reactions after immunization.Conclusions. Where the final intention is to use MVA after FP9 priming, previous testing of MVA alone overestimates reactogenicity. These recombinant vectors appear to be safe and suitable for use in larger- scale studies of children in Africa and of HIV-positive individuals.