Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in Combination with Plasmid Interleukin 12 and Impact of Intramuscular Electroporation for Delivery
Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in Combination with Plasmid Interleukin 12 and Impact of Intramuscular Electroporation for Delivery
复制标题
DOI：
10.1093/infdis/jit236
复制
发表时间：
2013-09-01
影响因子：
6.4
通讯作者：
Weiner, David B.
中科院分区：
文献类型：
--
作者：
Kalams, Spyros A.;Parker, Scott D.;Weiner, David B.
背景资料。DNA疫苗在人类中的免疫原性很差，但在Prime-Boost方案中已成为一种有效的启动方式，需要提高DNA疫苗的免疫原性的方法。方法：研究方法。HIV疫苗试验网络(HVTN)研究070和080是多中心、随机、临床试验。人类免疫缺陷病毒1型(HIV-1)PENNVAX(R)-B DNA疫苗(PV)是由编码HIV-1 B亚型包膜蛋白、GAG和POL的3个表达载体混合而成。白介素12(IL-12)DNA表达人IL-12蛋白p35和p40。研究对象为18-50岁的健康HIV-1未感染成年人。HVTN 070组肌肉接种4次，HVTN 080组肌肉接种3次后电穿孔接种。细胞内细胞因子染色检测HIV-1多肽池刺激后的细胞免疫反应。疫苗接种是安全的，耐受性良好。尽管接种的疫苗较少，但PV加IL-12与电穿孔联合使用具有显著的剂量节约效应，并且提供的免疫原性优于未使用电穿孔的试验中观察到的免疫原性。共71.4%的PV+IL-12电穿孔疫苗接种者在第二次免疫后出现了CD4(+)或CD8(+)T细胞应答，88.9%的人在第三次接种后出现了CD4(+)或CD8(+)T细胞应答。在PV注射后使用电穿孔比不使用电穿孔的注射提供更好的免疫原性。这项研究说明了组合DNA方法在人类中产生令人印象深刻的免疫反应的能力。
Background. DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens.Methods to increase the immunogenicity of DNA vaccines are needed. Methods. HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX(R)-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1-uninfected adults 18-50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools.Results. Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4(+) or CD8(+) T-cell response after the second vaccination, and 88.9% developed a CD4(+) or CD8(+) T-cell response after the third vaccination.Conclusions. Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.