Genetic stability of a recombinant adenovirus vaccine vector seed library expressing human papillomavirus type 16 E6 and E7 proteins

Wu,Jie; Chen,Ke‑Da; Gao,Meng; Chen,Gang; Jin,Su‑Feng; Zhuang,Fang‑Cheng; Wu,Xiao‑Hong; Jiang,Yun‑Shui; Li,Jian‑Bo

doi:10.3892/etm.2015.2268

April-2015 Volume 9 Issue 4

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April-2015 Volume 9 Issue 4

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Article

Genetic stability of a recombinant adenovirus vaccine vector seed library expressing human papillomavirus type 16 E6 and E7 proteins

Authors:
- Jie Wu
- Ke‑Da Chen
- Meng Gao
- Gang Chen
- Su‑Feng Jin
- Fang‑Cheng Zhuang
- Xiao‑Hong Wu
- Yun‑Shui Jiang
- Jian‑Bo Li
View Affiliations / Copyright

Affiliations: Institute of Viral Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310053, P.R. China
Pages: 1161-1165
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Published online on: February 5, 2015

https://doi.org/10.3892/etm.2015.2268
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Abstract

The aim of the present study was to understand the genetic stability of a master seed bank (MSB) and a working seed bank (WSB) of an adenovirus vector vaccine expressing the human papillomavirus (HPV) type 16 E6 and E7 fusion proteins (Ad‑HPV16E6E7). Microscopic examination and viral infectious efficacy were used to measure the infectious titers of the Ad‑HPV16E6E7 MSB and WSB. Polymerase chain reaction was used to analyze the stability of the Ad‑HPV16E6E7 target gene insertion, while western blot analysis and immunofluorescence were used to assess the expression levels of the Ad‑HPV16E6E7 target protein. A C57BL/6 mouse TC‑1 tumor cell growth inhibition model was used to evaluate the biological effect of Ad‑HPV16E6E7 administration. The infectious titers of the Ad‑HPV16E6E7 MSB and WSB were 6.31x109 IU/ml and 3.0x109 IU/ml, respectively. In addition, the expression levels of the inserted target genes and target proteins were found to be stable. In the mouse TC‑1 tumor inhibition analysis, when the virus titers of the Ad‑HPV16E6E7 MSB and WSB were 109 IU/ml, the tumor inhibition rate was 100%, which was significantly different when compared with the control group (χ2MSB=20.00 and χ2WSB=20.00; P<0.01). Therefore, the Ad‑HPV16E6E7 vaccine seed bank is genetically stable and meets the requirements for vaccine development.

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1	zur Hausen H: Papillomavirus infections - a major cause of human cancers. Biochem Biophys Acta. 1288:F55–F78. 1996.
2	Bosch FX, Lorincz A, Munoz N, Meijer CJ and Shan KV: The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 55:244–265. 2002. View Article : Google Scholar : PubMed/NCBI
3	zur Hausen H: Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2:342–350. 2002. View Article : Google Scholar : PubMed/NCBI
4	Roden RB, Ling M and Wu TC: Variation to prevent and treat cervical cancer. Hum Pathol. 35:971–982. 2004. View Article : Google Scholar : PubMed/NCBI
5	Murakami M, Ugai H, Wang M, Belousova N, Dent P, Fisher PB, Glasgow JN, Everts M and Curiel DT: An adenoviral vector expressing human adenovirus 5 and 3 fiber proteins for targeting heterogeneous cell populations. Virology. 407:196–205. 2010. View Article : Google Scholar : PubMed/NCBI
6	Ren J, Zhao L, Tian HW, Gao J, Feng J, Pang Z, Wu XB, Tan WJ and Ruan L: Immunogenicity and antitumor efficacy of the recombinant adenovirus expressing E7 and E6 fusion proteins of HPV type 16 in mice. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 32:276–280. 2012.(In Chinese).
7	China Food and Drug Administration. Human gene therapy research and drug preparation quality control technology guidelines. http://www.sda.gov.cn/WS01/CL0237/15708.htmluri. Accessed May 13, 2013
8	Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China 2010 (English edition). China Medical Science Press; Beijing: pp. 3–9. 2011
9	de Vrij J, Willemsen RA, Lindholm L and Hoeben RC; GIANT Consortium. Bangma CH, et al: Adenovirus-derived vectors for prostate cancer gene therapy. Hum Gene Ther. 21:795–805. 2010. View Article : Google Scholar
10	Jiang Y, Yin N, Bai L and Yuan XR: Effect observation of 9 cases patients with nasopharyngeal carcinoma locally injected with recombinant adenovirus 5. Bulletin of the Academy of Military Medical Science. 34:2152010.
11	Wang J: Biological Engineering Drugs Research Development and Quality Control. Science Press; Beijing: pp. 606–612. 2002
12	Smyth LJ, Van Poelgeest MI, Davidson EJ, et al: Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination. Clin Cancer Res. 10:2954–2961. 2004. View Article : Google Scholar : PubMed/NCBI