Details:

Alternative Title:
Virol J
Personal Author:
Zhao, Li ; Liu, Binlei ; Ren, Jiao ; Feng, Jing ; Pang, Zheng ; ... More +
Zhao, Li ; Liu, Binlei ; Ren, Jiao ; Feng, Jing ; Pang, Zheng ; Gao, Jian ; Zhang, Hui ; Tan, Wenjie ; Tian, Houwen ; Ruan, Li Less -
Description:
Background

Persistent infection with high-risk human papillomavirus (HPV) is a predominant cause of cervical cancer, and HPV16 and HPV18 occur in 50% and 20% of cervical cancer cases, respectively. The viral oncogenes E6 and E7 are constitutively expressed by HPV-associated tumour cells and can therefore be used as target antigens for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing the HPV16/18 E7E6 fusion proteins (rVVJ16/18E7E6) for use as a therapeutic vaccine for the treatment of HPV16+ and HPV18+ cancers.

Methods

We constructed a bivalent recombinant vaccinia virus expressing modified E7E6 fusion proteins of HPV type 16 and 18 (rVVJ16/18E7E6) based on the vaccinia virus Tiantan strain. We then defined the cellular immune responses to the virus in mice and rhesus monkeys and assessed antitumour efficacy of these responses in mice using the TC-1 tumour challenge model.

Results

Our data demonstrated that rVVJ16/18E7E6 was able to elicit varying levels of CD8+ T cell immune responses and lysis of target cells in mice in response to peptides HPV16E749-57 and HPV18E667-75. Furthermore, the virus was also able to induce anti-tumour responses in the HPV16+ TC-1 tumour challenge model, including partial protection (30-40%) and delayed tumour appearance. In addition, the virus was able to induce immune responses in rhesus monkeys.

Conclusions

The recombinant vaccinia virus rVVJ16/18E7E6 can generate clear and significant cellular immunity in both mice and rhesus monkeys. These data provide a basis for the use of this recombinant virus as a potential vaccine candidate for further study.


Subject:
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Animals Carcinoma CD8-Positive T-Lymphocytes Cell Line, Tumor Disease Models, Animal DNA-Binding Proteins Drug Carriers Female Genetic Vectors Macaca Mulatta Mice Mice, Inbred C57BL Oncogene Proteins, Viral Papillomavirus E7 Proteins Papillomavirus Vaccines Recombinant Fusion Proteins Repressor Proteins Research Rodent Diseases Treatment Outcome Vaccines, Synthetic Vaccinia Virus
Source:
Virol J. 2011; 8:302.
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:966cec218e3b6441036dc1b18133506e9d94195c4ba8560bb3e0f303f212e016
Download URL:
https://stacks.cdc.gov/view/cdc/3643/cdc_3643_DS1.pdf
File Type:

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