title: Strong immune responses induced by a DNA vaccine containing HPV16 truncated E7 C-terminal linked to HSP70 gene.
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 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.
  
  
  CONCLUSIONS
  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 DNA-based cancer vaccines.
authors.affiliation: Department of Virology, Tarbiat Modares University, Tehran, Iran. Soleim_h@modares.ac.ir
authors.forename: Zahra
authors.initials: Z
authors.lastname: Meshkat
authors.forename: Hoorieh
authors.initials: H
authors.lastname: Soleimanjahi
authors.forename: Hessam
authors.initials: H
authors.lastname: Mirshahabi
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Meshkat
authors.forename: Maryam
authors.initials: M
authors.lastname: Kheirandish
authors.forename: Zuhair Mohamad
authors.initials: ZM
authors.lastname: Hassan
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000276:immunology*; D017384:Sequence Deletion / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16