Hassan Syed Waqas, Waheed Mohammad Tahir, Müller Martin, Clarke Jihong Liu, Shinwari Zabta Khan, Lössl Andreas Günter
a Department of Biotechnology ; Quaid-i-Azam University ; Islamabad , Pakistan.
Hum Vaccin Immunother. 2014;10(10):2975-82. doi: 10.4161/21645515.2014.970973. Epub 2014 Nov 19.
Human Papillomavirus (HPV) is the main cause of cervical cancer, which is the second most severe cancer of women worldwide, particularly in developing countries. Although vaccines against HPV infection are commercially available, they are neither affordable nor accessible to women in low income countries e.g. Africa. Thus, alternative cost-effective vaccine production approaches need to be developed. This study uses tobacco plants to express pentameric capsomeres of HPV that have been reported to generate elevated immune responses against HPV. A modified HPV-16 L1 (L1_2xCysM) protein has been expressed as a fusion protein with glutathione-S-transferase (GST) in tobacco chloroplasts following biolistic transformation. In total 7 transplastomic lines with healthy phenotypes were generated. Site specific integration of the GST-L1_2xCysM and aadA genes was confirmed by PCR. Southern blot analysis verified homogenous transformation of all transplastomic lines. Antigen capture ELISA with the conformation-specific antibody Ritti01, showed protein expression as well as the retention of immunogenic epitopes of L1 protein. In their morphology, GST-L1 expressing tobacco plants were identical to wild type plants and yielded fertile flowers. Taken together, these data enrich knowledge for future development of cost-effective plant-made vaccines against HPV.
人乳头瘤病毒(HPV)是宫颈癌的主要病因,宫颈癌是全球女性中第二大致命癌症,在发展中国家尤为如此。尽管有针对HPV感染的疫苗可供商业使用,但低收入国家(如非洲)的女性既买不起也无法获得这些疫苗。因此,需要开发具有成本效益的替代疫苗生产方法。本研究利用烟草植株表达HPV的五聚体衣壳粒,据报道,该衣壳粒能产生增强的针对HPV的免疫反应。在生物弹道转化后,一种经过修饰的HPV-16 L1(L1_2xCysM)蛋白已在烟草叶绿体中作为与谷胱甘肽-S-转移酶(GST)的融合蛋白表达。总共产生了7个具有健康表型的转质体系。通过PCR确认了GST-L1_2xCysM和aadA基因的位点特异性整合。Southern印迹分析验证了所有转质体系的均匀转化。用构象特异性抗体Ritti01进行的抗原捕获ELISA显示了蛋白质表达以及L1蛋白免疫原性表位的保留。在形态上,表达GST-L1的烟草植株与野生型植株相同,并产生可育花。综上所述,这些数据丰富了未来开发具有成本效益的针对HPV的植物源疫苗的知识。