Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: Protection correlates with neutralizing antibody
Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: Protection correlates with neutralizing antibody
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DOI：
10.1016/j.vaccine.2012.04.046
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发表时间：
2012-06-13
期刊：
影响因子：
5.5
通讯作者：
Rose, John K.
中科院分区：
文献类型：
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作者：
Schell, John B.;Bahl, Kapil;Rose, John K.
在之前的疫苗研究中，我们报告了对高剂量、粘膜、猿猴免疫缺陷病毒（SIV）准种属攻毒的显著且明显的杀菌免疫[27]。该疫苗由基于表达猿猴免疫缺陷病毒（SIV）gag和env基因的水泡性口炎病毒（VSV）的载体、用表达相同Sly基因的繁殖复制子颗粒进行的加强、以及用基于VSV的载体进行的第二次加强组成。与该发表的研究同时，我们有一组平行的猕猴，给予相同剂量的疫苗载体，但另外，我们仅在引发免疫中包括表达恒河猴GM-CSF的第三种VSV载体。我们在这里报告，表达GM-CSF的载体的加入并没有增强CD 8 T细胞或抗体对Sly抗原的应答，并且几乎完全消除了疫苗对高剂量Sly粘膜攻击的保护。在猕猴模型中，GM-CSF的表达可能过度限制了载体复制。我们的研究结果表明，谨慎使用GM-CSF作为疫苗佐剂，特别是当表达的病毒载体。结合来自本研究和先前研究的疫苗组动物，我们发现在针对中和抗性SIV Env的中和抗体和保护免受感染之间存在边际但显著的正相关。(C)2012爱思唯尔有限公司保留所有权利。
In a previous vaccine study, we reported significant and apparently sterilizing immunity to high-dose, mucosal, simian immunodeficiency virus (SIV) quasi-species challenge [27]. The vaccine consisted of vectors based on vesicular stomatitis virus (VSV) expressing simian immunodeficiency virus (SIV) gag and env genes, a boost with propagating replicon particles expressing the same Sly genes, and a second boost with VSV-based vectors. Concurrent with that published study we had a parallel group of macaques given the same doses of vaccine vectors, but in addition, we included a third VSV vector expressing rhesus macaque GM-CSF in the priming immunization only. We report here that addition of the vector expressing GM-CSF did not enhance CD8 T cell or antibody responses to Sly antigens, and almost completely abolished the vaccine protection against high-dose mucosal challenge with Sly. Expression of GM-CSF may have limited vector replication excessively in the macaque model. Our results suggest caution in the use of GM-CSF as a vaccine adjuvant, especially when expressed by a viral vector. Combining vaccine group animals from this study and the previous study we found that there was a marginal but significant positive correlation between the neutralizing antibody to a neutralization resistant SIV Env and protection from infection. (C) 2012 Elsevier Ltd. All rights reserved.