Zahra Meshkat; Hoorieh Soleimanjahi; Hessam Mirshahabi; Mojtaba Meshkat; Maryam Kheiandish; Zuhair Mohammad Hassan
Volume 8, Issue 2 , June 2011, , Pages 65-75
Abstract
Background: Vaccines capable of controlling tumor virus based infections are found difficult to develop due to the consistence latent infection in the host. DNA vaccines are attractive tools for the development of HPV vaccines and inducing antigen-specific immunity owing to the stability, simplicity ...
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Background: Vaccines capable of controlling tumor virus based infections are found difficult to develop due to the consistence latent infection in the host. DNA vaccines are attractive tools for the development of HPV vaccines and inducing antigen-specific immunity owing to the stability, simplicity of delivery, safety and cost effectiveness. However, there is a need to increase their potency by procedures such as using HSP70 gene as an adjuvant. Objective: To evaluate a DNA vaccine containing HPV16 truncated E7 C-terminal cytotoxic T-lymphocyte epitopes linked to HSP70 gene (HSP70-tE7) in an animal model. Methods: Mice were immunized with the plasmid DNA after pre-treatment with cardiotoxin. The splenocytes of immunized mice were then tested for CTL activity by detecting the apoptosis and necrosis in target cells, cytokine production by ELISA, CD4 and CD8 frequencies by flow cytometry, and lymphocyte stimulation by MTT assay. Results: The recombinant expression vector was able to elicit immune responses close to that of full length E7 complete gene. Although the use of a small part of a target antigen can induce immune responses equivalent to the full length antigen, it fails to elicit statistically significant stronger immune responses when fused with HSP70 compared to the complete E7 gene alone. Conclusion: The potent immunogenicity of HPV16 E7 was preserved in the HSP70-tE7 vaccine and may represent a target of choice for the therapeutic vaccination strategies. However, to improve the immunogenicity polytope DNA vaccines which elicit multiple effector and memory CTL responses should be considered in future studies of DNAbased cancer vaccines.
Zahra Meshkat; Hoorieh Soleimajjahi; Mahmoud Mahmoudi; Zuhair Mohammad Hassan; Hessam Mirshahabi; Mojtaba Meshkat; Maryam Kheirandish
Abstract
Background: Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among female population worldwide. Specific human papillomaviruses and, most notably, HPV types 16 and 18 are recognized as being caus-ally associated with cervical carcinomas. The early ...
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Background: Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among female population worldwide. Specific human papillomaviruses and, most notably, HPV types 16 and 18 are recognized as being caus-ally associated with cervical carcinomas. The early HPV type 16 genes, E6 and E7, di-rectly participate in the in vitro transformation of primary human keratinocytes and rep-resent an excellent target for immune therapy of HPV related disease. Objective: The aim of this study was the evaluation of the efficacy of a DNA vaccine containing human papillomaviruse type 16 E7 gene (Iranian isolate) in induction of CTL responses in an animal model. Methods: In this study, the expression vector containing HPV type 16 E7 gene was constructed and chosen as a model antigen in the development of a thera-peutic DNA vaccine in an animal model. CTL responses, cytokine assay, lymphocyte stimulation test, CD4 and CD8 staining and flowcytometry were done for evaluating of the immune responses. Results: Our findings indicate that the target DNA vaccine can induce an E7-specific CTL response, which is important in the lysis of infected tumor cells, compared to negative control (p<0.005) after in vivo immunization in the mouse system. Conclusion: The developed vaccine may be promising as an anti-cancer vac-cine.