Ahn Julie, Peng Shiwen, Hung Chien-Fu, Roden Richard B S, Wu Tzyy-Choou, Best Simon R
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, U.S.A.
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, U.S.A.
Laryngoscope. 2017 Dec;127(12):2713-2720. doi: 10.1002/lary.26737. Epub 2017 Jul 17.
OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus (HPV) types 6 and 11. Although a prophylactic vaccine against RRP is available, a therapeutic vaccine is needed to treat those already infected. The objective of our study was to design and test a DNA vaccine targeting HPV11 proteins.
Preclinical scientific investigation.
A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated. Immunologic response to the HPV11 CRT/E6E7 vaccine was measured by vaccinating C57BL/6 mice via electroporation and measuring CD8 + T cell responses from harvested splenocytes. A tumor cell line containing HPV11-E6E7 was created, and the ability of novel DNA vaccine to control tumor growth was measured in vivo.
Our vaccine generated a significant and specific CD8 + T-cell response against the HPV11-E6aa41-70 peptide. The CD8 + T-cell responses did not recognize E7 epitopes, indicating E6 immunodominance. CD8 + responses were augmented in the CRT-linked vaccine compared to a control non-CRT vaccine. The HPV11 CRT/E6E7 vaccine was used to treat mice inoculated with a HPV11 E6E7 expressing tumor cell line after temporary CD3 depletion to facilitate tumor growth. Vaccinated mice had a significantly lower tumor growth rate (P = .029) and smaller tumor volumes compared to control mice, indicating an augmented immunologic response in vaccinated mice.
A DNA vaccine targeting HPV11 E6E7 generates a specific HPV11 CD-8 + T-cell response capable of reducing the growth of HPV11-expressing tumors. DNA vaccines are a promising immunologic strategy for treating RRP.
NA. Laryngoscope, 127:2713-2720, 2017.
目的/假设：复发性呼吸道乳头状瘤病（RRP）是一种由6型和11型人乳头瘤病毒（HPV）引起的良性疾病。尽管已有针对RRP的预防性疫苗，但仍需要一种治疗性疫苗来治疗已感染者。我们研究的目的是设计并测试一种针对HPV11蛋白的DNA疫苗。
临床前科学研究。
构建一种编码与钙网蛋白（CRT）相连的HPV11 E6和E7基因的DNA疫苗。通过电穿孔法给C57BL/6小鼠接种HPV11 CRT/E6E7疫苗，并检测收获的脾细胞中CD8 + T细胞反应，以此来测定对该疫苗的免疫反应。创建一种含有HPV11-E6E7的肿瘤细胞系，并在体内测定新型DNA疫苗控制肿瘤生长的能力。
我们的疫苗产生了针对HPV11-E6aa41-70肽的显著且特异性的CD8 + T细胞反应。CD8 + T细胞反应不识别E7表位，表明E6具有免疫优势。与对照非CRT疫苗相比，CRT相连疫苗中的CD8 +反应增强。在暂时耗竭CD3以促进肿瘤生长后，用HPV11 CRT/E6E7疫苗治疗接种了表达HPV11 E6E7的肿瘤细胞系的小鼠。与对照小鼠相比，接种疫苗的小鼠肿瘤生长速率显著更低（P = 0.029），肿瘤体积更小，表明接种疫苗的小鼠免疫反应增强。
一种针对HPV11 E6E7的DNA疫苗可产生特异性的HPV11 CD-8 + T细胞反应，能够减少表达HPV11的肿瘤的生长。DNA疫苗是治疗RRP的一种有前景的免疫策略。
无。《喉镜》，2017年，第127卷，第2713 - 2720页
