Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation
Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation
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DOI：
10.1016/j.vaccine.2010.11.011
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发表时间：
2011-01-17
期刊：
影响因子：
5.5
通讯作者：
Vasan, Sandhya
中科院分区：
文献类型：
--
作者：
Dolter, Karen E.;Evans, Claire F.;Vasan, Sandhya
ADVAX是一种基于DNA的候选HIV疫苗，在人体肌肉注射（IM）时安全但免疫原性较弱。在动物模型中进行了研究，以确定替代递送方法，体内电穿孔（EP）是否可以改善ADVAX的免疫原性，同时保持可接受的安全性。在第0、3和6周用ADVAX（有或没有EP）免疫小鼠，显示EP组中对所有抗原的γ干扰素ELISpot应答显著更高。通过细胞内细胞因子染色定量的抗原特异性CD 4+和CD 8 + T细胞应答均用EP显著改善。兔中ADVAX-EP重复给药毒性评价未发现任何安全性问题。ADVAX IM和EP给药在大鼠中的生物分布研究表明，两组中疫苗主要定位于给药部位。在第60天对残留质粒进行基于PCR的定量表明，IM和EP递送的整合事件进入宿主基因组的可能性较低。总之，这些数据支持在人类志愿者中使用EP递送的ADVAX的临床开发。(C)2010爱思唯尔有限公司保留所有权利。
ADVAX is a DNA-based candidate HIV vaccine that was safe but weakly immunogenic when delivered intramuscularly (IM) in humans. Studies were performed in animal models to determine whether an alternative delivery method, in vivo electroporation (EP), could improve the immunogenicity of ADVAX while maintaining an acceptable safety profile. Immunization of mice with ADVAX with or without EP at weeks 0, 3, and 6, revealed significantly higher gamma interferon ELISpot responses to all antigens in the EP groups. Antigen-specific CD4+ and CD8+ T cell responses, as quantified by intracellular cytokine staining, both improved significantly with EP. Evaluation of repeat-dose toxicity of ADVAX-EP in rabbits did not reveal any safety concerns. Biodistribution studies of ADVAX delivered IM and with EP in rats indicated that the vaccine was localized predominantly to the administration site in both groups. PCR-based quantitation of residual plasmid at Day 60 indicated that the potential for integration events into the host genome was low for both IM and EP delivery. Taken together, these data supported the clinical development of ADVAX delivered with EP in human volunteers. (C) 2010 Elsevier Ltd. All rights reserved.