title: Repeated DNA vaccinations elicited qualitatively different cytotoxic T lymphocytes and improved protective antitumor effects.
abstract: The use of DNA vaccines for generating antigen-specific CD8+ T cell responses has been well established. However, little is known about the quantitative and qualitative aspects of CD8+ T cell responses and protective immunity generated after repeated DNA vaccinations. We used human papillomavirus (HPV) type-16 E7 as a model tumor antigen in an E7-expressing tumor model, TC-1, to assess the influence of the frequency of DNA vaccinations on E7-specific immunological and antitumor responses. Mice were vaccinated with 1-4 inoculations of pcDNA 3-E7 DNA. Immunological assays and tumor protection experiments were performed to assess the effect of repeated E7 DNA vaccination on E7-specific T cells and E7-expressing tumors. Our results demonstrated that mice receiving an increased number of E7 DNA vaccinations exhibited higher E7-specific CTL activity, a rapid expansion of E7-specific IFN-gamma-secreting CD8+ T cells upon stimulation with E7 antigen, and a stronger antitumor effect against an E7-expressing tumor. Furthermore, we found that increasing the number of E7 DNA vaccinations followed by vaccinia booster enhanced the functional avidity of E7-specific CD8+ T cells. Our data suggest that quantitative and qualitative characteristics of antigen-specific CD8 + T cell responses and the ensuing protective antitumor effect can be influenced by the frequency of DNA vaccinations. These results have important clinical implications for the use of naked DNA vaccines in cancer immunotherapy.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: Sara I
authors.initials: SI
authors.lastname: Pai
authors.forename: Keng-Fu
authors.initials: KF
authors.lastname: Hsu
authors.forename: Liangmei
authors.initials: L
authors.lastname: He
authors.forename: Morris
authors.initials: M
authors.lastname: Ling
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000517:prevention & control / Q000628:therapy; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*
chemical_list: D000956:Antigens, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma