Browse > Article
http://dx.doi.org/10.4062/biomolther.2010.18.1.001

DNA Vaccines against Infectious Diseases and Cancer  

Han, Duk-Jae (Department of Microbiology, School of Medicine, Catholic University of Daegu)
Weiner, David B. (Department of Pathology and Laboratory Medicine, University of Pennsylvania)
Sin, Jeong-Im (Department of Microbiology, School of Medicine, Catholic University of Daegu)
Publication Information
Biomolecules & Therapeutics / v.18, no.1, 2010 , pp. 1-15 More about this Journal
Abstract
Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.
Keywords
Cancer; DNA vaccines; Infectious diseases;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 2  (Related Records In Web of Science)
Times Cited By SCOPUS : 1
연도 인용수 순위
1 Boyer, J. D., Ugen, K. E., Wang, B., Agadjanyan, M., Gilbert, L., Bagarazzi, M. L., Chattergoon, M., Frost, P., Javadian, A., Williams, W. V. and Refaeli, Y., Ciccarelli, R. B., McCallus, D., Coney, L. and Weiner, D. B. (1997a). Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. Nat. Med. 3, 526-532.   DOI
2 Condon, C., Watkins, S., Celluzzi, C., Thompson, K. and Faldo, L. (1996). DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2, 1122-1128.   DOI
3 Corr, M., Lee, D. J., Carson, D. A. and Tighe, H. (1996). Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J. Exp. Med. 184, 1555-1560.   DOI
4 Calarota, S. A., Hokey, D. A., Dai, A, Jure-Kunkel, M. N, Balimane, P. and Weiner, D. B. (2008). Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB costimulatory molecule. Vaccine 26, 3121-3134.   DOI
5 Chen, M. W., Cheng, T. J., Huang, Y., Jan, J. T., Ma, S. H., Yu, A. L., Wong, C. H. and Ho, D. D. (2008). A consensushemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc. Natl. Acad. Sci. USA 105, 13538-13543.   DOI
6 Capone, S., Zampaglione, I., Vitelli, A., Pezzanera, M., Kierstead, L., Burns, J., Ruggeri, L., Arcuri, M., Cappelletti, M., Meola, A., Ercole, B. B., Tafi, R., Santini, C., Luzzago, A., Fu, T. M., Colloca, S., Ciliberto, G., Cortese, R., Nicosia, A., Fattori, E. and Folgori, A. (2006). Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates. J. Immunol. 177, 7462-7471.   DOI
7 Rowland-Jones, S., Sutton, J., Ariyoshi, K., Dong, T., Gotch, F., McAdam, S., Whitby, D., Sabally, S., Gallimore, A., Corrah, T., Takiguchi, M., McMichael, A. and Whittle, H. (1995). HIV-specific T cells in HIV-exposed but uninfected Gambian women. Nature Med. 1, 59-64.   DOI
8 Scott, P., Natovitz, P., Coffman, R. L., Pearce, E. and Sher, A. (1988). Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J. Exp. Med. 168, 1675-1684.   DOI
9 Shiver, J. W., Davies, M. E., Perry, H. C., Freed, D. C. and Liu, M. A. (1996). Humoral and cellular immunuties elicited by HIV-1 vaccination. J. Pharm. Sci. 85, 1317-1324.   DOI
10 Sin, J. I., Kim, J. M., Bae, S. H., Lee, I. H., Park, J. S. and Ryoo, H. M. (2009a). Adoptive transfer of human papillomavirus E7-specific CTL enhances tumor chemoresponse through the perforin/granzyme-mediated pathway. Mol. Ther. 17, 906-913.   DOI
11 Sin, J. I. (2006a). Human paillomavirus vaccines for the treatment of cervical cancer. Exp. Rev. Vaccines 5, 783-792.   DOI
12 Sin, J. I. (2009b). Promises and challenges of human papillomavirus vaccines for cervical cancer. Exp. Rev. Anticancer Ther. 9, 1-5.   DOI
13 Sin, J. I., Hong, S. H., Park, Y. J., Park, J. B., Choi, Y. S. and Kim, M. S. (2006b). Antitumor therapeutic effects of E7 subunit and DNA vaccines in an animal cervical cancer model: antitumor efficacy of E7 therapeutic vaccines is dependent on tumor sizes, vaccine doses, and vaccine delivery routes. DNA & Cell Biol. 25, 277-286.   DOI
14 Choo, Q. L., Kuo, G., Ralston, R., Weiner, A., Chien, D., Van Nest, G., Han, J., Berger, K., Thudium, K., Kuo, C., Kansopon, J., McFarland, J., Tabrizi, A., Ching, K., Moss, B., Cummins, L. B., Houghton, M. and Muchmore, E. (1994). Vaccination of chimpanzees against infection by the hepatitis C virus. Proc. Natl. Acad. Sci. USA 91, 1294-1298.   DOI
15 Casares, S., Inaba, K., Brumeanu, T. D., Steinman, R. M. and Bona, C. A. (1997). Anitigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J. Exp. Med. 186, 1481-1486.   DOI
16 Chattergoon, M., Boyer, J. and Weiner, D. B. (1997). Genetic immunization: a new era in vaccines and immune therapies. FASEB J. 11, 753-763.   DOI
17 Folgori, A., Capone, S., Ruggeri, L., Meola, A., Sporeno, E., Ercole, B. B., Pezzanera, M., Tafi, R., Arcuri, M., Fattori, E., Lahm, A., Luzzago, A., Vitelli, A., Colloca, S., Cortese, R. and Nicosia, A. (2006). A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees. Nat. Med. 12, 190-7.   DOI
18 Chow, Y. H., Chiang, B. L., Lee, Y. L., Chi, W. K., Lin, W. C., Chen, Y. T. and Tao, M. H. (1998). Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J. Immunol. 160, 1320-1329.
19 Chu, R. S., Targoni, O. S., Krieg, A. M., Lehmann, P. V. and Harding, C. V. (1997). CpG oligonucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J. Exp. Med. 186, 1623-1631.   DOI
20 Cohen, A. D., Diab, A., Perales, M. A., Wolchok, J. D., Rizzuto, G., Merghoub, T., Huggins, D., Liu, C., Turk, M. J., Restifo, N. P., Sakaguchi, S. and Houghton, A. N. (2006). Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res. 66, 4904-12.   DOI
21 Sin, J. I., Kim, J. J., Zhang, D. H. and Weiner, D. B. (2001). Modulation of cellular responses by plasmid CD40L: CD40L plasmid vectors enhance antigen-specific helper T cell type 1 CD4+ T cell-mediated protective immunity against herpes simplex virus type 2 in vivo. Hum. Gene Ther. 12, 1091-1102.   DOI
22 Sin, J. I., Kim, J., Pachuk, C., Satishchanran, C. and Weiner, D. B. (2000). DNA vaccines encoding interleukin-8 and RANTES enhance antigen-specific Th-1 type CD4+ T cell-mediated protecetive immunity against herpes simplex virus-2 in vivo. J. Virol. 74, 11173-11180.   DOI
23 Sin, J. I., Kim, J. J., Arnold, R. L., Shroff, K. E., McCallus, D., Pachuk, C., McElhiney, S. P., Wolf, M. W., Pompa-de Bruin, S. J., Higgins, T. J., Ciccarelli, R. B. and Weiner, D. B. (1999a). Interleukin-12 gene as a DNA vaccine adjuvant in a herpes mouse model: IL-12 enhances Th1 type CD4+ T cell mediated protective immunity against HSV-2 challenge. J. Immunol. 162, 2912-2921.
24 Sin, J. I., Kim, J. J., Boyer, J. D., Higgins, T. J., Ciccarelli, R. B. and Weiner, D. B. (1999b). In vivo modulation of vaccineinduced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model. J. Virol. 73, 501-509.
25 Sin, J. I., Sung, J. H., Suh, Y. S., Lee, A. H., Chung, J. H., and Sung, Y. C. (1997). Protective immunity against heterologous challenge with encephalomyocarditis virus by VP1 DNA vaccination: effect of co-injection with a granulocyte, macrophage-colony stimulating factor gene. Vaccine 15, 1827-1833.   DOI
26 Sin, J. I., Ayyavoo, V., Boyer, J. D., Kim, J. J., Ciccarelli, R. B. and Weiner, D. B. (1999c). Protective immune correlates can segregate by vaccine type in a murine herpes model system. Int. Immunol. 11, 1763-1773.   DOI
27 Cuadros, C., Dominguez, A. L., Lollini, P. L., Croft, M., Mittler, R. S., Borgström, P. and Lustgarten, J. (2005). Vaccination with dendritic cells pulsed with apoptotic tumors in combination with anti-OX40 and anti-4-1BB monoclonal antibodies induces T cell-mediated protective immunity in Her-2/neu transgenic mice. Int. J. Cancer 116, 934-943.   DOI
28 Cohen, A. D., Boyer, J. D. and Weiner, D. B. (1998). Modulating the immune response to genetic immunization. FASEB J. 12, 1611-1626.   DOI
29 Comes, A., Rosso, O., Orengo, A. M., Di Carlo, E., Sorrentino, C., Meazza, R., Piazza, T., Valzasina, B., Nanni, P., Colombo, M. P. and Ferrini, S. (2006). CD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an IL-21-secreting cellular vaccine. J. Immunol. 176, 1750-1758.   DOI
30 Gronevik, E., von Steyern, F. V., Kalhovde, J. M., Tjelle, T. E. and Mathiesen, I. (2005). Gene expression and immune response kinetics using electroporation-mediated DNA delivery to muscle. J. Gene Med. 7, 218-227.   DOI
31 Davis, H. L., McCluskie, M. J., Gerin, J. L. and Purcell, R. H. (1996). DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc. Natl. Acad. Sci. USA 93, 7213-7218.   DOI
32 Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., Lennon, V. A., Celis, E. and Chen, L. (2002). Tumor associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793-800.   DOI
33 Dreesman, G. R., Hollinger, F. B., Sanchez, Y., Oefinger, P. and Melnick, J. L. (1981). Immunization of chimpanzees with hepatitis B virus derived polypeptides. Infect. Immunity 32, 62-67.
34 Sumida, S. M., McKay, P. F., Truitt, D. M., Kishko, M. G., Arthur, J. C., Seaman, M. S., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Letvin, N. L., and Barouch, D. H. (2004). Recruitment and expansion of dendritic cells in vivo potentiate the immunogenicity of plasmid DNA vaccines. J. Clin. Investig. 114, 1334-1342.   DOI
35 Smahel, M., Sima, P., Ludvikova, V. and Vonka, V. (2001). Modified HPV16 E7 genes as DNA vaccine against E7-containing oncogenic cells. Virology 281, 231-238.   DOI
36 Strasser, J. E., Arnold, R. L., Pachuk, C., Higgins, T. J. and Bernstein, D. I. (2000). Herpes simplex virus DNA vaccine efficacy: effect of glycoprotein D plasmid constructs. J. Infect. Dis. 182, 1311-1320.   DOI
37 Strome, S. E., Dong, H. D., Tamura, H. H., Voss, S. G., Flies, D. B., Tamada, K., Salomao, D., Cheville, J., Hirano, F., Lin, W., Kasperbauer, J. L., Ballman, K. V. and Chen, L. (2003). B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res. 63, 6501-6505.
38 Toka, F. N., Gierynska, M. and Rouse, B. T. (2003). Codelivery of CCR7 ligands as molecular adjuvants enhances the protective immune response against herpes simplex virus type 1. J. Virol. 77, 12742-12752.   DOI
39 van Elsas, A., Hurwitz, A. A. and Allison, J. P. (1999). Combination immunotherapy of B16 melanoma using anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 190, 355-366.   DOI
40 Encke, J., Putlitz, J. Z., Geissler, M. and Wands, J. R. (1998). Genetic immunization generates cellular and humoral immune responses against the nonstructural proteins of the hepatitis C virus in a murine model. J. Immunol. 161, 4917-4923.
41 Feltquate, D. M., Heaney, S., Webster, R. G. and Robinson, H. L. (1997). Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158, 2278-2284.
42 Hinkula, J., Lundholm, P. and Wahren, B. (1997). Nucleic acid vaccination with HIV regulatory genes: a combination of HIV-1 genes in separate plasmids induces strong immune responses. Vaccine 15, 874-878.   DOI
43 Fournillier, A., Nakano, I., Vitvitski, L., Depla, E., Vidalin, O., Maertens, G., Trepo, C. and Inchauspe, G. (1998). Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes. Hepatol. 28, 237-244.   DOI
44 Frelin, L., Ahlen, G., Alheim, M., Weiland, O., Barnfield, C., Liljestrom, P. and Sällberg, M. (2004). Codon optimization and mRNA amplification effectively enhances the immunogenicity of the hepatitis C virus nonstructural 3/4A gene. Gene Ther. 11, 522-33.   DOI
45 Fynan, E. F., Webster, R. G., Fuller, D. H., Haynes, J. R., Santoro, J. C. and Robinson, H. L. (1993). DNA vaccines: protective immunization by parenteral, mucosal, and genesun inoculations. Proc. Natl. Acad. Sci. USA 90, 11478-11482.   DOI
46 Geng, H., Zhang, G. M., Xiao, H., Yuan, Y., Li, D., Zhang, H., Qiu, H., He, Y. F. and Feng, Z. H. (2006). HSP70 vaccine in combination with gene therapy with plasmid DNA encoding sPD-1 overcomes immune resistance and suppresses the progression of pulmonary metastatic melanoma. Int. J. Cancer 118, 2657-2664.   DOI
47 Wang, R., Doolan, D. L., Le, T. P., Hedstrom, R. C., Coonan, K. M., Charoenvit, Y., Jones, T. R., Hobart, P., Margalith, M., Ng, J., Weiss, W. R., Sedegah, M., de Taisne, C., Norman, J. A. and Hoffman, S. L. (1998). Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science 282, 476-480.   DOI
48 Viehl, C. T., Moore, T. T., Liyanage, U. K., Frey, D. M., Ehlers, J. P., Eberlein, T. J., Goedegebuure, P. S. and Linehan, D. C. (2006). Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancerbearing mice. Ann. Surg. Oncol. 13, 1252-1258.   DOI
49 Wang, B., Boyer, J. D., Srikantan, V., Coney, L., Carrano, R., Phan, C., Merva, M., Dang, K., Agadjanyan, M. G., Ugen, K. E., Williams, W. V. and Weiner, D. B. (1993a). DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and non-human primates. DNA and Cell Biology 12, 799-805.   DOI
50 Wang, B., Ugen, K. E., Srikantan, V., Agadjanyan, M. G., Dang, K., Refaeli, Y., Sato, A., Boyer, J., Williams, W. V. and Weiner, D. B. (1993b). Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 90, 4156-4160.   DOI
51 Weiner, D. B. and Sin, J. I. (2005). Opposite roles of B7.1 and CD28 costimulatory molecules for protective immunity against HSV-2 challenge in a gD DNA vaccine model. Immune Network 5, 68-77.   DOI
52 Yamano, T., Kaneda, Y., Huang, S., Hiramatsu, S. H. and Hoon, D. S. (2006). Enhancement of immunity by a DNA melanoma vaccine against TRP2 with CCL21 as an adjuvant. Mol. Ther. 13, 194-202.   DOI   ScienceOn
53 Guidotti, L. G., Ando, K., Hobbs, M. V., Ishikawa, T., Runkel, L., Schreiber, R. D. and Chisari, F. V. (1994). Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc. Natl. Acad. Sci. USA 91, 3764-3768.   DOI
54 Germann, T., Gately, M. K., Schoenhaut, D. S., Lohoff, M., Mattner, F., Fischer, S., Jin, S. C., Schmitt, E. and Rude, E. (1993). Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells. Eur. J. Immunol. 23, 1762-1770.   DOI
55 Gramzinski, R. A., Millan, C. L., Obaldia, N., Hoffman, S. L. and Davis, H. L. (1998). Immune response to a hepatitis B DNA vaccine in Aotus monkeys: a comparison of vaccine formulation, route, and method of administration. Mol. Med. 4, 109-118.
56 Iwasaki, A., Torres, C. A., Ohashi, P. S., Robinson, H. L. and Barber, B. H. (1997). The dominant role of bone marrowderived cells in CTL induction following plasmid DNA immunization at different sites. J. Immunol. 158, 685-692.
57 He, Y. F., Zhang, G. M., Wang X. H., Zhang H., Yuan, Y., Li, D. and Feng, Z. H. (2004). Blocking programmed death (PD)-Ligand-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine. J. Immunol. 173, 4919-4928.   DOI
58 Halwani, R., Boyer, J. D., Yassine-Diab, B., Haddad, E. K., Robinson, T. M., Kumar, S., Parkinson, R., Wu, L., Sidhu, M. K., Phillipson-Weiner, R., Pavlakis, G. N., Felber, B. K., Lewis, M. G., Shen, A., Siliciano, R. F., Weiner, D. B. and Sekaly, R. P. (2008). Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA + IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques. J. Immunol. 180, 7969-7979.   DOI
59 Ye, G. W., Park, J. B., Park, Y. J., Choi, Y. S. and Sin, J. I. (2007). Increased sensitivity of radiated murine cervical cancer tumors to E7 subunit vaccine-driven CTL-mediated killing induces synergistic antitumor activity. Mol. Ther. 15, 1564-1570.   DOI
60 Yang, S. H., Lee, C. G., Park, S. H., Im, S. J., Kim, Y. M., Son, J. M., Wang, J. S., Yoon, S. K., Song, M. K., Ambrozaitis, A., Kharchenko, N., Yun, Y. D., Kim, C. M., Kim, C. Y., Lee, S. H., Kim, B. M., Kim, W. B. and Sung, Y. C. (2006). Correlation of antiviral T-cell responses with suppression of viral rebound in chronic hepatitis B carriers: a proof-ofconcept study. Gene Ther. 13, 1110-1117.   DOI
61 Zhang, H., Snyder, K. M., Suhoski, M. M., Maus, M. V., Kapoor, V., June, C. H. and Mackall, C. L. (2007). 4-1BB is superior to CD28 costimulation for generating CD8+ cytotoxic lymphocytes for adoptive immunotherapy. J. Immunol. 179, 4910-4918.   DOI
62 Hirao, L. A., Wu, L., Khan, A. S., Hokey, D. A., Yan, J., Dai, A., Betts, M. R., Draghia-Akli, R. and Weiner, D. B. (2008a). Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques. Vaccine 26, 3112-3120.   DOI
63 Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L. and Locksley, R. M. (1989). Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J. Exp. Med. 169, 59-72.   DOI
64 Higgins, T. J., Herold, K. M., Arnold, R. L., McElhiney, S. P., Shroff, K. E. and Pachuk, C. J. (2000). Plasmid DNAexpressed secreted and nonsecreted forms of herpes simplex virus glycoprotein D2 induce different types of immune responses. J. Infect. Dis. 182, 1311-1320.   DOI
65 Hirano, F., Kaneko, K., Tamura, H., Dong, H., Wang, S., Ichikawa, M., Rietz, C., Flies, D. B., Lau, J. S., Zhu, G., Tamada, K. and Chen, L. (2005). Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 65, 1089-1096.
66 Hooper, J. W., Golden, J. W., Ferro, A. M. and King, A. D. (2007). Smallpox DNA vaccine delivered by novel skin electroporation device protects mice against intranasal poxvirus challenge. Vaccine 25, 1814-1823.   DOI
67 Hsu, K. F., Hung, C. F., Cheng, W. F., He, L., Slater, L. A., Ling, M. and Wu, T. C. (2001). Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen. Gene Ther. 8, 376-383.   DOI
68 Hung, C. F., Cheng, W. F., Hsu, K. F., Chai, C. Y., He, L., Ling, M. and Wu, T. C. (2001). Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigen. Cancer Res. 61, 3698-3703.
69 Hung, C. F., Cheng, W. F., He, L., Ling, M., Juang, J., Lin, C. T. and Wu, T. C. (2003). Enhancing major histocompatibility complex class I antigen presentation by targeting antigen to centrosomes. Cancer Res. 63, 2393-2398.
70 Widera, G., Austin, M., Rabussay, D., Goldbeck, C., Barnett, S. W., Chen, M., Leung, L., Otten, G. R., Thudium, K., Selby, M. J. and Ulmer, J. B. (2000). Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J. Immunol. 164, 4635-4640.   DOI
71 Hung, C. F., He, L., Juang, J., Lin, T. J., Ling, M., and Wu, T. C. (2002). Improving DNA vaccine potency by linking Marek's disease virus type 1 VP22 to an antigen. J. Virol. 76, 2676-2682.   DOI
72 Jakob, T., Walker, P. S., Krieg, A. M., Udey, M. C. and Vogel, J. C. (1998). Activation of cutaneous dendritic cells by CpG-containing oligonucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA. J. Immunol. 161, 3042-3049.
73 Ji, H., Wang, T. L., Chen, C. H., Pai, S. I., Hung, C. F., Lin, K. Y., Kurman, R. J., Pardoll, D. M. and Wu, T. C. (1999). Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors. Hum. Gene Ther. 10, 2727-2740.   DOI
74 Kalat, M., Kupcu, Z., Schuller, S., Zalusky, D., Zehetner, M., Paster, W. and Schweighoffer, T. (2002). In vivo plasmid electroporation induces tumor antigen-specific CD8+ T-cell responses and delays tumor growth in a syngeneic mouse melanoma model. Cancer Res. 62, 5489-5494.
75 Kawagoe, T., Takeuchi, O., Takabatake, Y., Kato, H., Isaka, Y., Tsujimura, T. and Akira, S. (2009). TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis. Nat. Immunol. 10, 965-972.   DOI   ScienceOn
76 Kim, J. J., Trivedi, N. N. Wilson, D. M. Mahalingam, S., Morrison, L., Tsai, A., Chattergoon, M. A., Dang, K., Patel, M., Ahn, L., Boyer, J. D., Chalian, A. A., Schoemaker, H., Kieber-Emmons, T., Agadjanyan, M. and Weiner, D. B. (1998b). Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine. Oncogene 17, 3125-3135.   DOI
77 Kim, C. Y., Kang, E. S., Kim, S. B., Kim, H. E., Choi, J. H., Lee, D. S., Im, S. J., Yang, S.H., Sung, Y. C., Kim, B. M. and Kim, B. G. (2008). Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation. Exp. Mol. Med. 40, 669-676.   DOI
78 Kim, J. J., Nottingham, L. K., Sin, J. I. Tsai, A., Morrison, L., Dang, K., Hu, Y., Kazahaya, K., Bennett, M., Dentchev, T., Wilson, D. M., Chalian, A. A., Boyer, J. D., Agadjanyan, M. G. and Weiner, D. B. (1998a). CD8 positive T-cells influence antigen-specific immune responses through the expression of chemokines. J. Clin. Invest. 102, 1112-1124.   DOI
79 Kim, J. J., Bagarazzi, M. L., Trivedi, N., Hu, Y., Chattergoon, M. A., Dang, K., Mahalingam, S., Agadjanyan, M. G., Boyer, J. D., Wang, B. and Weiner, D. B. (1997a). Engineering of in vivo immune responses to DNA immunization via co-delivery of costimulatory molecule genes. Nature Biotech. 15, 641-645.   DOI
80 Kim, J. J., Ayyavoo, V., Bagarazzi, M. L., Chattergoon, M. A., Dang, K., Wang, B., Boyer, J. D. and Weiner, D. B. (1997b). In vivo engineering of a cellular immune response by co-administration of IL-12 expression vector with a DNA immunogen. J. Immunol. 158, 816-826.
81 Kim, M. S. and Sin, J. I. (2005). Both antigen optimization and lysosomal targeting are required for enhanced anti-tumour protective immunity in a human papillomavirus E7-expressing animal tumour model. Immunol. 116, 255-266.   DOI   ScienceOn
82 Kuklin, N. A., Daheshia, M., Karem, K., Manickan, E. and Rouse, B. T. (1997). Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization. J. Virol. 71, 3138-3145.
83 Kim, T. Y., Myoung, H. J., Kim, J. H., Moon, I. S., Kim, T. G., Ahn W. S. and Sin, J. I. (2002). Both E7 and CpG-ODN are required for protective immunity against challenge with human papillomavirus 16 (E6/E7)-immortalized tumor cells: Involvement of CD4+ and CD8+ T cells in protection. Cancer Res. 62, 7234-7240.
84 Klinman, D. M., Yamshchikov, G. and Ishigatsubo, Y. (1997). Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158, 3635-3639.
85 Krieg, A. M., Love-Homan, L., Yi, A. K. and Harty, J. T. (1998). CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenges. J. Immunol. 161, 2428-2434.
86 Kutzler, M. A., Kraynyak, K. A., Nagle, S. J., Parkinson, R. M., Zharikova, D., Chattergoon, M., Maguire, H., Muthumani, K., Ugen, K. and Weiner, D. B. (2009). Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo. Gene Ther. In press.
87 Laddy, D. J., Yan, J., Khan, A. S., Andersen, H., Cohn, A., Greenhouse, J., Lewis, M., Manischewitz, J., King, L. R., Golding, H., Draghia-Akli, R. and Weiner, D. B. (2009). Electroporation of synthetic DNA antigens offers protection in nonhuman primates challenged with highly pathogenic avian influenza virus. J. Virol. 83, 4624-4630.   DOI
88 Laddy, D. J., Yan, J., Kutzler, M., Kobasa, D., Kobinger, G. P., Khan, A. S., Greenhouse, J., Sardesai, N. Y., Draghia-Akli, R. and Weiner, D. B. (2008). Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens. PLoS One 3, e2517.   DOI
89 Leclerc, C., Deriaud, E., Rojas, M. and Whalen, R. G. (1997). The preferential induction of Th1 immune response by DNA-based immunization is mediated by the immunostimulatory effect of plasmid DNA. Cell. Immunol. 179, 97-106.   DOI
90 Lagging, L. M., Meyer, K., Hoft, D., Houghton, M., Belshe, R. B. and Ray, R. (1995). Immune responses to plasmid DNA encoding the hepatitis C virus core protein. J. Virol. 69, 5859-5863.
91 Leitner, W. W., Sequin, M. C., Ballou, W. R., Seitz, J. P., Schultz, A. M., Sheehy, M. J. and Lyon, J. A. (1997). Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites. J. Immunol. 159, 6112-6119.
92 Levy, M. Y., Barron, L. G., Meyer, K. B. and Szoka, F. C. Jr. (1996). Characterization of plasmid DNA transfer into mouse skeletal muscle: evaluation of uptake mechanism, expression and secretion of gene products into blood. Gene Therapy 3, 201-211.
93 Liu, J., Kjeken, R., Mathiesen, I. and Barouch, D. H. (2008). Recruitment of antigen-presenting cells to the site of inoculation and augmentation of human immunodeficiency virus type 1 DNA vaccine immunogenicity by in vivo electroporation. J. Virol. 82, 5643-5649.   DOI
94 Lohr, F., Lo, D. Y., Zaharoff, D. A., Hu, K., Zhang, X., Li, Y., Zhao, Y., Dewhirst, M. W., Yuan, F. and Li, C. Y. (2001). Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation. Cancer Res. 61, 3281-3284.
95 Lucas, M. L., Heller, L., Coppola, D. and Heller, R. (2002). IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma. Mol. Ther. 5, 668-75.   DOI
96 Luxembourg, A., Evans, C. F. and Hannaman, D. (2007). Electroporationbased DNA immunization: translation to the clinic. Expert Opin. Biol. Ther. 7, 1647-1664.   DOI
97 Aihara, H. and Miyazaki, J. (1998). Gene transfer into muscle by electroporation in vivo. Nat. Biotechnol. 16, 867-870.   DOI
98 Barouch, D. H. (2006). Rational design of gene-based vaccines. J. Pathol. 208, 283-289.   DOI
99 Bae, S. H., Park, Y. J., Choi, Y. S., Park, J. B., Kim, M. S. and Sin, J. I. (2007). Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in an animal tumor model: causal involvement of increased sensitivity of cisplatintreated tumors to CTL-mediated killing in therapeutic synergy. Clin. Cancer Res. 13, 341-349.   DOI
100 Luckay, A., Sidhu, M. K., Kjeken, R., Megati, S., Chong, S. Y., Roopchand, V., Garcia-Hand, D., Abdullah, R., Braun, R., Montefiori, D. C., Rosati, M., Felber, B. K., Pavlakis, G. N., Mathiesen, I., Israel, Z. R., Eldridge, J. H. and Egan, M. A. (2007). Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J. Virol. 81, 5257-5269.   DOI
101 MacGregor, R. R., Boyer, J. D., Ugen, K. E., Lacy, K. E., Gluckman, S. J., Bagarazzi, M. L., Chattergoon, M. A., Baine, Y., Higgins, T. J., Ciccarelli, R. B., Coney, L. R., Ginsberg, R. S. and Weiner, D. B. (1998). First clinical trial of a DNA-based vaccine for treatment of HIV-1 infection: safety and host response. J. Infect. Dis. 178, 92-100.   DOI   ScienceOn
102 Purcell, R. H. and Gerin, J. L. (1975). Hepatitis B subunit vaccine: a preliminary report of safety and efficacy tests in chimpanzees. Am. J. Med. Sci. 270, 395-399.   DOI   ScienceOn
103 Major, M. E., Vitvitski, L., Mink, M. A., Schleef, M., Whalen, R. G., Trepo, C. and Inchauspe, G. (1995). DNA-based immunization with chimeric vectors for the induction of immune responses against the hepatitis C virus nucleocapsid. J. Virol. 69, 5798-5805.
104 Manato, T., Shibata, R., Siemon, C., Connors, M., Lane, H. C. and Martin, M. A. (1998). Adminitration of anti-CD8 monoclonal antibody interferes with the clearance of chimeric simian/human immunodeficiency virus during primary infections of rhesus macaques. J. Virol. 72, 164-169.
105 Mancini, M., Hadchouel, M., Davis, H. L., Whalen, R. G., Tiollais, P. and Michel, M. L. (1996). DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state. Proc. Natl. Acad. Sci. USA 93, 12496-12501.   DOI
106 Mendoza, R. B., Cantwell, M. J. and Kipps, T. J. (1997). Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene immunization. J. Immunol. 159, 5777-5781.
107 Boyer, J. D., Ugen, K. E., Chattergoon, M., Wang, B., Shah, A., Agadjanyan, M., Bagarazzi, M. L., Javadian, A., Carrano, R., Coney, L., Williams, W. V. and Weiner, D. B. (1997b). DNA vaccination as anti-human immunodeficiency virus immunotherapy in infected chimpanzees. J. Infec. Dis. 176, 1501-1509.   DOI
108 Buchan, S., Gronevik, E., Mathiesen, I., King, C. A., Stevenson, F. K. and Rice, J. (2005). Electroporation as a “prime/boost” strategy for naked DNA vaccination against a tumor antigen. J. Immunol. 174, 6292-6298.   DOI
109 McDonnell, W. M. and Askari, F. K. (1996). Molecular medicine: DNA vaccines. New Eng. J. Med. 334, 42-45.   DOI
110 McKay, P. F., Barouch, D. H., Santra, S., Sumida, S. M., Jackson, S. S., Gorgone, D. A., Lifton, M. A. and Letvin, N. L. (2004). Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4 and CD8 T lymphocyte responses. Eur. J. Immunol. 34, 1011-1020.   DOI
111 Myers, L., Lee, S. W., Rossi R. J., Lefrancois, L., Kwon, B. S., Mittler, R. S., Croft, M. and Vella, A. T. (2006). Combined CD137 (4-1BB) and adjuvant therapy generates a developing pool of peptide-specific CD8 memory T cells. Int. Immunol. 18, 325-333.   DOI
112 Roos, A. K., Moreno, S., Leder, C., Pavlenko, M., King, A. and Pisa, P. (2006). Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol. Ther. 13, 320-327.   DOI
113 Okada, E., Sasaki, S., Ishii, N., Aoki, I., Yasuda, T., Nishioka, K., Fukushima, J. Miyazaki, J., Wahren, B. and Okuda, K. (1997). Intranasal immunization of a DNA vaccine with IL-12-and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J. Immunol. 159, 3638-3647.
114 Peggs, K. S., Quezada, S. A., and Allison, J. P. (2009). Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists. Clin. Exp. Immunol. 157, 9-19.   DOI
115 Barouch, D. H., Santra, S., Tenner-Racz, K., Racz, P., Kuroda, M. J., Schmitz, J. E., Jackson, S. S., Lifton, M. A., Freed, D. C., Perry, H. C., Davies, M. E., Shiver, J. W. and Letvin, N. L. (2002). Potent CD4 T-cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing gp120 and GM-CSF. J. Immunol. 168, 562-568.   DOI
116 Ahlen, G., Soderholm, J., Tjelle, T., Kjeken, R., Frelin, L., Hoglund, U., Blomberg, P., Fons, M., Mathiesen, I. and Sallberg, M. (2007). In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells. J. Immunol. 179, 4741-4753.   DOI
117 Chen, S. C., Jones, D. H., Fynan, E. F., Farrar, G. H., Clegg, J. C. and Greenberg, H. B. (1998). Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles. J. Virol. 72, 5757-5761.
118 Cheng, W. F., Hung, C. F., Chai, C. Y., Hsu, K. F., He, L., Ling, M. and Wu, T. C. (2001). Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J. Clin. Invest. 108, 669-678.   DOI
119 Barrett, N., Eder, G. and Dorner, F. (1991). Characterization of a vaccinia-derived recombinant HIV-1 gp160 candidate vaccine and its immunogenicity in chimpanzees. Biotech. Therapeu. 2, 91-106.
120 Bodles-Brakhop, A. M., Heller, R. and Draghia-Akli, R. (2009). Electroporation for the delivery of DNA-based vaccines and mmunotherapeutics: current clinical developments. Mol. Ther. 17, 585-592.   DOI
121 Boyer, J. D., Wang, B., Ugen, K. E., Agadjanyan, M., Javadian, A., Frost, P., Dang, K., Carrano, R. A., Ciccarelli, R., Coney, L., Williams, W. V. and Weiner, D. B. (1996). In vivo protective anti-HIV immune responses in non-human primates through DNA immunization. J. Med. Primat. 25, 242-250.   DOI   ScienceOn
122 Prayaga, S. K., Ford, M. J. and Haynes, J. R. (1997). Manipulation of HIV-1 gp120-specific immune responses elicited via gene gun-based DNA immunizattion. Vaccine 15, 1349-1352.   DOI
123 Pentcheva-Hoang, T., Corse, E. and Allison, J. P. (2009). Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections. Immunol. Rev. 229, 67-87.   DOI
124 Pertmer, T. M., Eisenbraun, M. D., McCabe, D., Prayaga, S. K., Fuller, D. H. and Haynes, J. R. (1995). Gene gun-based nucleic acid immunization; elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13, 1427-1430.   DOI
125 Prasad, S. J., Farrand, K. J., Matthews, S. A., Chang, J. H., McHugh, R. S. and Ronchese, F. (2005). Dendritic cells loaded with stressed tumor cells elicit long-lasting protective tumor immunity in mice depleted of CD4+CD25+ regulatory T cells. J. Immunol. 174, 90-98.   DOI
126 Quezada, S. A., Peggs, K. S., Curran, M. A. and Allison, J. P. (2006). CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J. Clin. Invest. 116, 1935-1945.   DOI
127 Ray, N. B., Ewalt, L. C. and Lodmell, D. L. (1997). Nanogram quantities of plasmid DNA encoding the rabies virus glycoprotein protects mice against lethal rabies virus infection. Vaccine 15, 892-895.   DOI
128 Raz, E., Tighe, H., Sato, Y., Corr, M., Dudler, J. A., Roman, M., Swain, S. L., Spiegelberg, H. L. and Carson, D. A. (1996). Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc. Natl. Acad. Sci. USA 93, 5141-5145.   DOI
129 Rizzuto, G., Cappelletti, M., Maione, D., Savino, R., Lazzaro, D., Costa, P., Mathiesen, I., Cortese, R., Ciliberto, G., Laufer, R., La Monica, N. and Fattori, E. (1999). Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation. Proc. Natl. Acad. Sci. USA 96, 6417-6422.   DOI
130 Rerks-Ngarm, S., Pitisuttithum, P., Nitayaphan, S., Kaewkungwal, J., Chiu, J., Paris, R., Premsri, N., Namwat, C., de Souza, M., Adams, E., Benenson, M., Gurunathan, S., Tartaglia, J., McNeil, J. G., Francis, D. P., Stablein, D., Birx, D. L., Chunsuttiwat, S., Khamboonruang, C., Thongcharoen, P., Robb, M. L., Michael, N. L., Kunasol, P., Kim, J. H.; MOPH-TAVEG Investigators (2009). Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209-2220.   DOI
131 Roman, M., Martin-Orozco, E., Goodman, J. S., Nguyen, M. D., Sato, Y., Ronaghy, A., Kornbluth, R. S., Richman, D. D., Carson, D. A. and Raz, E. (1997). Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat. Med. 3, 849-854.   DOI
132 Roos, A. K., Pavlenko, M., Charo, J., Egevad, L. and Pisa, P. (2005). Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine. Prostate 62, 217-223.   DOI
133 Rosati, M., Bergamaschi, C., Valentin, A., Kulkarni, V., Jalah, R., Alicea, C., Patel, V., von Gegerfelt, A. S., Montefiori, D. C., Venzon, D. J., Khan, A. S., Draghia-Akli, R., Van Rompay, K. K., Felber, B. K. and Pavlakis, G. N. (2009). DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge. Proc. Natl. Acad. Sci. USA 106, 15831-15836.   DOI
134 Rosenberg, E. S., Billingsley, J. M., Caliendo, A. M., Boswell, S. L., Sax, P. E., Kalams, S. A. and Walker, B. D. (1997). Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447-1450.   DOI
135 Wells, D. J. (1993). Improved gene transfer by direct plasmid injection associated with regeneration in mouse skeletal muscle. FEBS 332, 179-182.   DOI
136 Hirao, L. A., Wu, L., Khan, A. S., Satishchandran, A., Draghia-Akli, R. and Weiner, D. B. (2008b). Intradermal/subcutaneous immunization by electroporation improves plasmid vaccine delivery and potency in pigs and rhesus macaques. Vaccine 26, 440-448.   DOI
137 Rowland-Jones, S., Dixon, D. F., Aldhous, M. C., Gotch, F., Ariyoshi, K., Hallam, N., Kroll, J. S., Froebal, K. and McMichael, A. (1993). HIV-specific cytotoxic T cell activity in an HIV-exposed but uninfected infant. Lancet 341, 860-861.   DOI
138 Cui, F. D., Asada, H., Jin, M. L., Kishida, T., Shin-Ya, M., Nakaya, T., Kita, M., Ishii, M., Iwai, M., Okanoue, T., Imanishi, J. and Mazda, O. (2005). Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice. Gene Ther. 12, 160-168.   DOI
139 Sin, J. I., Hong, S. H., Park, Y. J., Park, J. B., Choi, Y. S. and Kim, M. S. (2006b). Antitumor therapeutic effects of E7 subunit and DNA vaccines in an animal cervical cancer model: antitumor efficacy of E7 therapeutic vaccines is dependent on tumor sizes, vaccine doses, and vaccine delivery routes. DNA & Cell Biol. 25, 277-286.   DOI