Coutant Frédéric, Frenkiel Marie-Pascale, Despres Philippe, Charneau Pierre
Laboratoire de Virologie Moléculaire et Vectorologie, Institut Pasteur, Paris, France.
PLoS One. 2008;3(12):e3973. doi: 10.1371/journal.pone.0003973. Epub 2008 Dec 19.
Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogens because of their ability to initiate potent and durable specific immune responses. Strategies that alleviate safety concerns will facilitate the clinical developments involving lentiviral vectors. In this respect, the development of integration deficient lentiviral vectors circumvents the safety concerns relative to insertional mutagenesis and might pave the way for clinical applications in which gene transfer is targeted to non-dividing cells. We thus evaluated the potential use of nonintegrative lentiviral vectors as vaccination tools since the main targeted cell in vaccination procedures is the non-dividing dendritic cell (DC). In this study, we demonstrated that a single administration of nonintegrative vectors encoding a secreted form of the envelope of a virulent strain of West Nile Virus (WNV) induces a robust B cell response. Remarkably, nonintegrative lentiviral vectors fully protected mice from a challenge with a lethal dose of WNV and a single immunization was sufficient to induce early and long-lasting protective immunity. Thus, nonintegrative lentiviral vectors might represent a safe and efficacious vaccination platform for the development of prophylactic vaccines against infectious agents.
慢病毒载体因其能够引发强大而持久的特异性免疫反应，作为针对肿瘤和侵袭性病原体的独特候选病毒载体疫苗正受到密切关注。减轻安全担忧的策略将促进涉及慢病毒载体的临床开发。在这方面，整合缺陷型慢病毒载体的开发规避了与插入诱变相关的安全问题，并可能为基因转移靶向非分裂细胞的临床应用铺平道路。由于疫苗接种程序中的主要靶细胞是非分裂树突状细胞（DC），因此我们评估了非整合型慢病毒载体作为疫苗接种工具的潜在用途。在本研究中，我们证明单次给予编码西尼罗河病毒（WNV）毒株分泌形式包膜的非整合载体可诱导强烈的B细胞反应。值得注意的是，非整合型慢病毒载体可使小鼠完全免受致死剂量WNV的攻击，单次免疫足以诱导早期和持久的保护性免疫。因此，非整合型慢病毒载体可能代表一种安全有效的疫苗接种平台，用于开发针对感染因子的预防性疫苗。
