title: DNA vaccines: ready for prime time?
abstract: Since the discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and elicit an immune response, there has been much progress in understanding the basic biology of this platform. A large amount of data has been generated in preclinical model systems, and more sustained cellular responses and more consistent antibody responses are being observed in the clinic. Four DNA vaccine products have recently been approved, all in the area of veterinary medicine. These results suggest a productive future for this technology as more optimized constructs, better trial designs and improved platforms are being brought into the clinic.
authors.affiliation: Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kutzler
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000820:Animal Diseases / Q000628:therapy; D000818:Animals; D002986:Clinical Trials as Topic / Q000639:trends* / Q000662:veterinary; D004353:Drug Evaluation, Preclinical / Q000639:trends; D006801:Humans; D007109:Immunity / Q000502:physiology; D007167:Immunotherapy / Q000639:trends / Q000662:veterinary; D008954:Models, Biological; D019444:Vaccines, DNA / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019444:Vaccines, DNA
references.citation: J Anim Sci. 2006 Mar;84(3):733-42
references.pmid: 16478966
references.citation: J Virol. 2003 Jan;77(1):489-98
references.pmid: 12477854
references.citation: Science. 1998 Oct 16;282(5388):476-80
references.pmid: 9774275
references.citation: Nature. 1992 Mar 12;356(6365):152-4
references.pmid: 1545867
references.citation: J Infect Dis. 2006 Dec 15;194(12):1638-49
references.pmid: 17109335
references.citation: Vaccine. 2000 May 8;18(22):2337-44
references.pmid: 10738089
references.citation: Virology. 2007 Mar 30;360(1):218-34
references.pmid: 17097711
references.citation: J Immunol. 2005 May 15;174(10):6292-8
references.pmid: 15879128
references.citation: Immunol Rev. 1999 Aug;170:135-49
references.pmid: 10566148
references.citation: Ann N Y Acad Sci. 1995 Nov 27;772:30-9
references.pmid: 8546411
references.citation: Viral Immunol. 2005;18(1):205-12
references.pmid: 15802965
references.citation: Nature. 1975 Aug 7;256(5517):495-7
references.pmid: 1172191
references.citation: Vaccine. 2004 Jun 30;22(20):2517-23
references.pmid: 15193376
references.citation: Ann N Y Acad Sci. 1995 Nov 27;772:170-7
references.pmid: 8546390
references.citation: Nature. 2002 Jan 17;415(6869):331-5
references.pmid: 11797011
references.citation: J Biotechnol. 2003 Apr 24;102(2):105-15
references.pmid: 12697387
references.citation: Melanoma Res. 2000 Dec;10(6):577-83
references.pmid: 11198480
references.citation: Vaccine. 2005 May 31;23(29):3800-7
references.pmid: 15893617
references.citation: Virology. 2002 Oct 10;302(1):155-63
references.pmid: 12429524
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):16028-33
references.pmid: 15520369
references.citation: Dev Biol (Basel). 2006;126:261-70; discussion 327
references.pmid: 17058502
references.citation: Virology. 2007 Sep 15;366(1):197-211
references.pmid: 17499328
references.citation: Methods Mol Med. 2006;127:363-74
references.pmid: 16988466
references.citation: J Exp Med. 1998 Sep 21;188(6):1075-82
references.pmid: 9743526
references.citation: Vaccine. 2005 Feb 3;23(11):1384-92
references.pmid: 15661387
references.citation: Bioelectrochemistry. 2007 May;70(2):269-74
references.pmid: 17118714
references.citation: Emerg Infect Dis. 2002 Dec;8(12):1379-84
references.pmid: 12498651
references.citation: Intervirology. 2000;43(4-6):273-81
references.pmid: 11251382
references.citation: Dev Biol (Basel). 2000;104:33-43
references.pmid: 11713822
references.citation: FASEB J. 2006 Sep;20(11):1762-74
references.pmid: 16940148
references.citation: Adv Drug Deliv Rev. 2005 Jan 10;57(3):377-90
references.pmid: 15560947
references.citation: Expert Rev Vaccines. 2002 Oct;1(3):265-76
references.pmid: 12901567
references.citation: Proc Natl Acad Sci U S A. 1993 May 1;90(9):4156-60
references.pmid: 8483929
references.citation: Adv Genet. 2005;55:25-40
references.pmid: 16291211
references.citation: J Am Vet Med Assoc. 2005 Jan 15;226(2):240-5
references.pmid: 15706975
references.citation: J Immunol. 2004 Jul 1;173(1):550-8
references.pmid: 15210816
references.citation: Expert Rev Vaccines. 2007 Oct;6(5):747-59
references.pmid: 17931155
references.citation: Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777-81
references.pmid: 6294651
references.citation: Hum Mol Genet. 1997 Sep;6(9):1435-43
references.pmid: 9285779
references.citation: Microbes Infect. 2000 Nov;2(14):1677-85
references.pmid: 11137041
references.citation: AIDS Res Hum Retroviruses. 2003 Sep;19(9):817-23
references.pmid: 14585212
references.citation: Virology. 2000 Jul 5;272(2):417-28
references.pmid: 10873786
references.citation: N Engl J Med. 2005 Apr 7;352(14):1411-2
references.pmid: 15814877
references.citation: Biochem Biophys Res Commun. 2006 Oct 13;349(1):69-78
references.pmid: 16930549
references.citation: J Immunol. 2004 Aug 1;173(3):1941-50
references.pmid: 15265928
references.citation: Expert Opin Drug Deliv. 2007 May;4(3):197-213
references.pmid: 17489649
references.citation: J Med Primatol. 1997 Feb-Apr;26(1-2):27-33
references.pmid: 9271186
references.citation: J Clin Virol. 2004 Dec;31 Suppl 1:S99-106
references.pmid: 15567101
references.citation: Vaccine. 2004 Jul 29;22(21-22):2776-82
references.pmid: 15246611
references.citation: J Clin Invest. 2008 Apr;118(4):1427-36
references.pmid: 18324335
references.citation: J Control Release. 2006 Jul 20;113(3):261-70
references.pmid: 16793161
references.citation: Methods Mol Med. 2006;127:73-82
references.pmid: 16988447
references.citation: Hum Gene Ther. 1996 May 20;7(8):893-9
references.pmid: 8727503
references.citation: Gene Ther. 1999 Oct;6(10):1768-73
references.pmid: 10516727
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11307-11
references.pmid: 8248244
references.citation: Vaccine. 2008 Jun 13;26(25):3112-20
references.pmid: 18430495
references.citation: Gene Ther. 2004 Mar;11(6):522-33
references.pmid: 14999224
references.citation: Vaccine. 2007 Jun 28;25(27):5071-85
references.pmid: 17543427
references.citation: Vaccine. 2000 Jun 15;18(25):2779-88
references.pmid: 10812219
references.citation: Chin Med J (Engl). 2007 Mar 20;120(6):496-502
references.pmid: 17439744
references.citation: Vaccine. 2007 Feb 26;25(10):1814-23
references.pmid: 17240007
references.citation: Hum Vaccin. 2007 Sep-Oct;3(5):157-64
references.pmid: 17637571
references.citation: Dev Biol (Basel). 2000;104:53-6
references.pmid: 11713824
references.citation: J Infect Dis. 2000 Jan;181(1):406
references.pmid: 10608800
references.citation: Clin Cancer Res. 2005 Mar 1;11(5):1941-52
references.pmid: 15756020
references.citation: Vaccine. 2007 Sep 4;25(36):6635-45
references.pmid: 17669562
references.citation: Nat Rev Cancer. 2008 Feb;8(2):108-20
references.pmid: 18219306
references.citation: Infect Immun. 2005 Apr;73(4):2005-11
references.pmid: 15784541
references.citation: J Infect Dis. 1998 Jul;178(1):92-100
references.pmid: 9652427
references.citation: J Med Virol. 1990 May;31(1):13-7
references.pmid: 2142957
references.citation: Eur Urol. 2000 Aug;38(2):208-17
references.pmid: 10895014
references.citation: J Chin Med Assoc. 2006 Jan;69(1):7-13
references.pmid: 16447920
references.citation: Mol Ther. 2006 Feb;13(2):320-7
references.pmid: 16185933
references.citation: Viral Immunol. 2005;18(4):678-88
references.pmid: 16359234
references.citation: Cancer Treat Rev. 2003 Oct;29(5):371-87
references.pmid: 12972356
references.citation: DNA Cell Biol. 2006 Jul;25(7):383-92
references.pmid: 16848679
references.citation: Biotechnol J. 2008 Jan;3(1):83-9
references.pmid: 17806101
references.citation: Vaccine. 2000 Mar 17;18(18):1893-901
references.pmid: 10699338
references.citation: Mol Ther. 2006 Jan;13(1):194-202
references.pmid: 16112911
references.citation: Expert Opin Biol Ther. 2003 Oct;3(7):1083-92
references.pmid: 14519073
references.citation: Vaccine. 2004 Mar 29;22(11-12):1457-64
references.pmid: 15063569
references.citation: Nat Med. 1996 Oct;2(10):1122-8
references.pmid: 8837611
references.citation: Gene. 2001 Jul 11;272(1-2):149-56
references.pmid: 11470520
references.citation: Vaccine. 2004 Dec 9;23(4):460-9
references.pmid: 15530694
references.citation: Virology. 2006 Sep 1;352(2):438-49
references.pmid: 16780913
references.citation: J Virol. 2007 May;81(10):5257-69
references.pmid: 17329330
references.citation: Toxicol Sci. 2006 Jun;91(2):610-9
references.pmid: 16569729
references.citation: Hum Gene Ther. 1996 Jun 20;7(10):1205-17
references.pmid: 8793545
references.citation: Nucleic Acids Res. 1981 Nov 25;9(22):6047-68
references.pmid: 6273820
references.citation: Virology. 1999 Jun 20;259(1):148-53
references.pmid: 10364499
references.citation: Vaccine. 2006 Mar 15;24(12):2017-26
references.pmid: 16414158
references.citation: Science. 1993 Mar 19;259(5102):1745-9
references.pmid: 8456302
references.citation: AIDS Res Hum Retroviruses. 2004 Dec;20(12):1335-47
references.pmid: 15650426
references.citation: Immunol Rev. 2004 Jun;199:113-25
references.pmid: 15233730
references.citation: Cancer Gene Ther. 2001 Jun;8(6):405-13
references.pmid: 11498760
references.citation: Vaccine. 2006 May 22;24(21):4531-40
references.pmid: 16140431
references.citation: Vaccine. 2006 May 22;24(21):4565-8
references.pmid: 16154246
references.citation: Trends Biotechnol. 2004 Jul;22(7):346-53
references.pmid: 15245907
references.citation: Vaccine. 2007 Mar 1;25(11):2064-73
references.pmid: 17239494
references.citation: Vaccine. 1999 Apr 9;17(15-16):2036-42
references.pmid: 10217604
references.citation: Vaccine. 2007 Apr 20;25(16):3070-4
references.pmid: 17292518
references.citation: J Virol. 2005 Jul;79(13):8189-200
references.pmid: 15956564
references.citation: Vaccine. 2002 May 6;20(15):1995-8
references.pmid: 11983261
references.citation: Vaccine. 2008 Jan 17;26(3):440-8
references.pmid: 18082294
references.citation: Dis Aquat Organ. 2005 Apr 6;64(1):13-22
references.pmid: 15900683
references.citation: Vaccine. 2002 May 6;20(15):1975-9
references.pmid: 11983257
references.citation: J Virol. 2005 Jul;79(14):8828-34
references.pmid: 15994776
references.citation: Dev Biol (Basel). 2000;104:45-51
references.pmid: 11713823
references.citation: Vaccine. 2007 Mar 1;25(11):2120-7
references.pmid: 17250931
references.citation: Infect Immun. 2003 Sep;71(9):4961-9
references.pmid: 12933838
references.citation: Front Biosci. 2008 Jan 01;13:1711-5
references.pmid: 17981662
references.citation: Vaccine. 2006 May 22;24(21):4503-9
references.pmid: 16181711
references.citation: Vaccine. 2005 Mar 18;23(17-18):2136-48
references.pmid: 15755584
references.citation: Science. 2000 Oct 20;290(5491):486-92
references.pmid: 11039923
references.citation: Vet Microbiol. 2002 Aug 25;88(2):127-51
references.pmid: 12135633
references.citation: Gene Ther. 1995 Dec;2(10):710-22
references.pmid: 8750010
references.citation: Vaccine. 2007 Apr 20;25(16):2984-2989
references.pmid: 17306909
references.citation: Biochem Biophys Res Commun. 2004 Jan 2;313(1):89-96
references.pmid: 14672702
references.citation: DNA Cell Biol. 1993 Nov;12(9):777-83
references.pmid: 8216848
references.citation: Intervirology. 2000;43(4-6):258-72
references.pmid: 11251381
references.citation: Vaccine. 2001 Oct 12;20(1-2):42-8
references.pmid: 11567744
references.citation: Infect Immun. 2004 Aug;72(8):4707-15
references.pmid: 15271932
references.citation: Expert Opin Biol Ther. 2003 Sep;3(6):985-93
references.pmid: 12943457
references.citation: J Immunol. 2005 Jul 1;175(1):112-23
references.pmid: 15972637
references.citation: J Infect Dis. 2006 Dec 15;194(12):1650-60
references.pmid: 17109336
references.citation: Cell. 1985 Jun;41(2):521-30
references.pmid: 2985280
references.citation: Biomed Pharmacother. 2006 Sep;60(8):458-62
references.pmid: 16930935
references.citation: Biochim Biophys Acta. 2000 Jul 3;1475(2):125-32
references.pmid: 10832026
references.citation: EMBO J. 1997 May 1;16(9):2482-92
references.pmid: 9171361
references.citation: Annu Rev Immunol. 1997;15:617-48
references.pmid: 9143702
references.citation: Ann N Y Acad Sci. 1995 Nov 27;772:140-51
references.pmid: 8546386
references.citation: Pharm Res. 1999 Jun;16(6):889-95
references.pmid: 10397610
references.citation: Methods. 2006 Sep;40(1):10-9
references.pmid: 16997709
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11478-82
references.pmid: 8265577
references.citation: Vaccine. 1999 Jul 16;17(22):2826-9
references.pmid: 10438052
references.citation: Trends Mol Med. 2006 May;12(5):216-22
references.pmid: 16621717
references.citation: Methods. 2006 Sep;40(1):86-97
references.pmid: 16997717
references.citation: Immunol Rev. 2004 Jun;199:156-80
references.pmid: 15233733
references.citation: Nucleic Acids Res. 2001 Mar 1;29(5):E26
references.pmid: 11222777
references.citation: Vaccine. 2007 Jan 26;25(7):1316-27
references.pmid: 17052812
references.citation: Hybridoma (Larchmt). 2005 Dec;24(6):305-8
references.pmid: 16332197
references.citation: J Virol. 2004 Sep;78(17):9174-89
references.pmid: 15308713
references.citation: Int J Pharm. 2006 Feb 3;308(1-2):61-8
references.pmid: 16356671
references.citation: Infect Immun. 2001 Dec;69(12):7250-3
references.pmid: 11705894
references.citation: Nat Med. 2003 Jun;9(6):729-35
references.pmid: 12766765
references.citation: Curr HIV Res. 2007 Nov;5(6):507-13
references.pmid: 18045108
references.citation: Vaccine. 2007 Apr 30;25(17):3277-83
references.pmid: 17257714
references.citation: Cancer Res. 2004 Apr 15;64(8):2858-64
references.pmid: 15087404
references.citation: Exp Dermatol. 2007 Sep;16(9):724-9
references.pmid: 17697144
references.citation: Vaccine. 2006 May 22;24(21):4582-5
references.pmid: 16188351
references.citation: J Immunol. 2006 Nov 15;177(10):7462-71
references.pmid: 17082666
references.citation: J Immunol. 2002 Jun 1;168(11):5499-506
references.pmid: 12023344
references.citation: Vaccine. 2006 Feb 20;24(8):1225-34
references.pmid: 16219399
references.citation: Vaccine. 2002 Sep 10;20(27-28):3322-31
references.pmid: 12213402
references.citation: PLoS One. 2008 Jun 25;3(6):e2517
references.pmid: 18575608
references.citation: Vaccine. 2005 Sep 23;23(40):4867-78
references.pmid: 15985318
references.citation: Mol Ther. 2007 Feb;15(2):411-21
references.pmid: 17235321
references.citation: Hum Gene Ther. 2002 Sep 1;13(13):1551-60
references.pmid: 12228010
references.citation: Vaccine. 2004 Dec 16;23(5):629-38
references.pmid: 15542183
references.citation: Adv Drug Deliv Rev. 2001 Nov 19;52(3):197-207
references.pmid: 11718944