Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Vaccine. 2017 Dec 19;35(52):7240-7249. doi: 10.1016/j.vaccine.2017.11.011. Epub 2017 Nov 22.
In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines.
体内电穿孔 (EP) 重新激发了人们对 DNA 疫苗作为控制不同类型癌症的免疫治疗方法的临床兴趣。EP 与增强免疫反应效力有关，但它影响免疫调节的能力尚不清楚。在这里，我们评估了体内 EP 对针对人乳头瘤病毒诱导肿瘤的 DNA 疫苗诱导细胞免疫反应和治疗效果的影响。我们的结果表明，EP 与常规的肌肉内给药途径联合使用可促进多功能和效应记忆 CD8 T 细胞的更有效激活，增强细胞毒性活性。此外，EP 增加了肿瘤浸润的 CD8 T 细胞并避免了肿瘤复发。最后，我们的结果表明，EP 促进了抗原呈递细胞的局部迁移，并且随着疫苗共递送而增强。总之，这些证据进一步阐明了体内电穿孔的作用及其对 DNA 疫苗免疫原性的影响。
