IMT504:一种新的有效的狂犬病疫苗佐剂,可显著节省剂量

A. Montaner, Analia De Nichilo, Jose Rodriguez, A. Hernando-Insúa, J. Fló, R. López, V. Sierra, C. Paolazzi, O. Larghi, D. Horn, J. Zorzópulos, F. Elías
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引用次数: 8

摘要

背景:狂犬病毒感染引起脑炎,几乎总是致命的。疫苗接种在预防疾病方面非常有效,但费用过高。能够节省剂量和较少接种、抗体反应更快的疫苗配方将是非常可取的。IMT504是一种免疫刺激非cpg寡聚脱氧核苷酸,是一种高效的疫苗佐剂。方法:测定人和大鼠抗体,并进行大鼠激射试验。结果:在大鼠中,即使将疫苗稀释到1/625,也能观察到IMT504的高效免疫反应。在高致死率的脑内狂犬病活体攻击研究中,即使使用极稀释的疫苗加IMT504也能产生保护作用。在人体内,imt504佐剂稀释疫苗与非佐剂疫苗(全强度或稀释)相比,抗体滴度发展更快,且显著更高。5种经imt504佐剂稀释疫苗在第二次注射后均达到保护抗体(≥0.5 IU/ml)。在第三次注射后,接受imt504佐剂稀释疫苗的个体的水平比对照组高约10倍(M±SEM: 31.0±10.9 vs 3.40±0.99 IU/ml)。结论:这些数据表明,IMT504可以减少接种次数,高度显着的疫苗剂量节约,快速产生抗体和预防狂犬病。需要进行广泛的临床研究,以确认使用IMT504是否能够大大增加获得高效救生狂犬病疫苗的机会。
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IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing
Background: Rabies virus infection causes encephalitis, which is almost always fatal. Vaccination can be extremely effective at preventing disease but is prohibitively costly. Vaccine formulations allowing dose-sparing and fewer inoculations with faster antibody response would be extremely desirable. IMT504, an immunostimulatory non-CpG oligo-deoxynucleotide, is a highly potent vaccine adjuvant. Methods: Human and rat antibody measurements, and rat chal-lenge studies were performed. Results: In rats, highly effective immune responses with IMT504 were observed even after diluting vaccine up to 1/625. In highly lethal, live intracerebral rabies challenge studies, protection occurred even with extremely dilute vaccine plus IMT504. In humans, antibody titers developed faster and were significantly higher with IMT504-adjuvanted diluted vaccine vs non-adjuvanted vaccine (full strength or diluted). All five administered IMT504-adjuvanted diluted vaccine reached protective antibodies (≥0.5 IU/ml) after the second injection. After the third injection, individuals receiving IMT504-adjuvanted diluted vaccine reached levels approximately 10 times higher than controls (M ± SEM: 31.0 ± 10.9 vs 3.40 ± 0.99 IU/ml). Conclusions: These data suggest that IMT504 may allow fewer inoculations, highly significant dose-sparing of vaccine, rapid antibody production and protection from rabies. Extensive clinical studies are necessary to confirm if the use of IMT504 will permit significantly greater access to highly effective life-saving rabies vaccines.
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