Highly potent delivery method of gp160 envelope vaccine combining lentivirus-like particles and DNA electrotransfer

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• 作者：Gaë ; lle Vandermeulen^a ; ^b ; Takis Athanasopoulos^a ; ¹ ; Anita Trundley^a ; ¹ ; Keith Foster^a ; Vé ; ronique Pré ; at^b ; Rafael J. Yá ; ñ ; ez-Muñ ; oz^a ; George Dickson^a ; ^{g.dickson@rhul.ac.uk}
• 关键词：VLP ; Electroporation ; Electrotransfer ; HIV vaccine ; DNA vaccine
• 刊名：Journal of Controlled Release
• 出版年：2012
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：10 May, 2012
• 卷：159
• 期：3
• 页码：376-383
• 文件大小：696 K

摘要

Particulate antigen assemblies in the nanometer range and DNA plasmids are particularly interesting for designing vaccines. We hypothesised that a combination of these approaches could result in a new delivery method of gp160 envelope HIV-1 vaccine which could combine the potency of virus-like particles (VLPs) and the simplicity of use of DNA vaccines. Characterisation of lentivirus-like particles (lentiVLPs) by western blot, dynamic light scattering and electron microscopy revealed that their protein pattern, size and structure make them promising candidates for HIV-1 vaccines. Although all particles were similar with regard to size and distribution, they clearly differed in p24 capsid protein content suggesting that Rev may be required for particle maturation and Gag processing. In vivo, lentiVLP pseudotyping with the gp160 envelope or with a combination of gp160 and VSV-G envelopes did not influence the magnitude of the immune response but the combination of lentiVLPs with Alum adjuvant resulted in a more potent response. Interestingly, the strongest immune response was obtained when plasmids encoding lentiVLPs were co-delivered to mice muscles by electrotransfer, suggesting that lentiVLPs were efficiently produced in vivo or the packaging genes mediate an adjuvant effect. DNA electrotransfer of plasmids encoding lentivirus-like particles offers many advantages and appears therefore as a promising delivery method of HIV-1 vaccines.