Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis
Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis
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DOI：
10.1016/j.vaccine.2009.10.045
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发表时间：
2009-12-11
期刊：
影响因子：
5.5
通讯作者：
Piazza, Franco M.
中科院分区：
文献类型：
--
作者：
Velez, Ivan D.;Gilchrist, Katherine;Piazza, Franco M.
根据Montenegro皮肤试验（MST），对无利什曼病史的健康哥伦比亚成年志愿者既往利什曼原虫亚临床感染的证据进行评价。12名MST阳性受试者参加开放标签、非对照临床试验（“MST阳性试验”），并接受三次LEISH-F1 + MPL-SE疫苗（由10 μ g重组利什曼原虫多蛋白LEISH-F1抗原[TSA + LmSTI 1 + LeIF]+25 μ g MPL（R）-SE佐剂组成）的注射。68名MST阴性受试者参加了一项随机、双盲、对照试验（“MST阴性试验”），并被随机分配接受三次疫苗注射（n = 34）、10 μ g LEISH-F1蛋白单独注射（n = 17）或生理盐水安慰剂注射（n = 17）。在这两项试验中，在第0、28和56天皮下注射研究注射剂，并对受试者进行安全性和免疫学终点随访。在MST阳性和MST阴性受试者中，LEISH-F1 + MPL-SE疫苗安全且耐受性良好。在两项试验中，在超过一半的疫苗接种者中观察到第84天IFN-γ对LEISH-F1抗原的应答。在MST阴性试验中，IFN-γ应答在疫苗接受者中比在单独蛋白质或安慰剂接受者中显著更频繁和更大幅度。在所有疫苗接种者中观察到对LEISH-F1的IgG抗体应答。在这两项试验中，在大多数疫苗接种者中观察到对LEISH-F1的迟发型超敏反应（DTH）。在MST阴性试验中，接种疫苗的DTH显著高于安慰剂接种者。这些首次确定的利什曼病疫苗的临床试验表明，LEISH-F1 + MPL-SE疫苗在既往有或无利什曼原虫亚临床感染证据的健康受试者中是安全和免疫原性的。(C)2009爱思唯尔有限公司保留所有权利。
Healthy Colombian adult volunteers with no history of leishmaniasis were evaluated for evidence of previous subclinical infection with Leishmania based on the Montenegro skin test (MST). Twelve MST-positive subjects were enrolled in an open-label, uncontrolled clinical trial (the "MST-positive trial") and received three injections of the LEISH-F1 + MPL-SE vaccine (consisting of 10 mu g recombinant Leishmania polyprotein LEISH-F1 antigen [TSA + LmSTI1 + LeIF] + 25 mu g MPL (R)-SE adjuvant). Sixty-eight MST-negative subjects were enrolled in a randomized, double-blind, controlled trial (the "MST-negative trial") and were randomly assigned to receive three injections of either the vaccine (n = 34), 10 mu g LEISH-F1 protein alone (n = 17), or saline placebo (n = 17). In both trials, the study injections were given subcutaneously on Days 0, 28, and 56, and subjects were followed for safety and immunological endpoints. The LEISH-F1 + MPL-SE vaccine was safe and well tolerated in MST-positive and MST-negative subjects. In both trials, an IFN-gamma response to the LEISH-F1 antigen at Day 84 was observed in more than half of the vaccine recipients. In the MST-negative trial, the IFN-gamma response was significantly more frequent and of greater magnitude in vaccine recipients than in protein-alone or placebo recipients. An IgG antibody response to LEISH-F1 was observed in all vaccine recipients. In both trials, delayed-type hypersensitivity (DTH) to LEISH-F1 was observed in most of the vaccine recipients. In the MST-negative trial, DTH was significantly higher in vaccine than placebo recipients. These clinical trials of the first defined vaccine for leishmaniasis show that the LEISH-F1 + MPL-SE vaccine is safe and immunogenic in healthy subjects with and without evidence of previous subclinical infection with Leishmania. (C) 2009 Elsevier Ltd. All rights reserved.