A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques.
A candidate vaccine (D1ME-VRP) expressing dengue virus type 1 premembrane and envelope proteins in a Venezuelan equine encephalitis (VEE) virus replicon particle (VRP) system was constructed and tested in conjunction with a plasmid DNA vaccine (D1ME-DNA) expressing identical dengue virus sequences. Cynomolgus macaques were vaccinated with three doses of DNA (DDD), three doses of VRP (VVV group), or a heterologous DNA prime-VRP boost regimen (DDV) using two doses of DNA vaccine and a third dose of VRP vaccine. Four weeks after the final immunization, the DDV group produced the highest dengue virus type 1-specific immunoglobulin G antibody responses and virus-neutralizing antibody titers. Moderate T-cell responses were demonstrated only in DDD- and DDV-vaccinated animals. When vaccinated animals were challenged with live virus, all vaccination regimens showed significant protection from viremia. DDV-immunized animals were completely protected from viremia (mean time of viremia = 0 days), whereas DDD- and VVV-vaccinated animals had mean times of viremia of 0.66 and 0.75 day, respectively, compared to 6.33 days for the control group of animals.
Chen
Lan
L
Viral and Rickettsial Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Ewing
Dan
D
Subramanian
Hemavathy
H
Block
Karla
K
Rayner
Jonathan
J
Alterson
Kimberly D
KD
Sedegah
Martha
M
Hayes
Curtis
C
Porter
Kevin
K
Raviprakash
Kanakatte
K
D000818:Animals; D004267:DNA Viruses / Q000737:chemistry*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics*; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007107:Immune System; D007114:Immunization; D007074:Immunoglobulin G / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D008251:Macaca; D008297:Male; D012093:Replicon; D013601:T-Lymphocytes / Q000821:virology; D014765:Viral Vaccines / Q000737:chemistry*
D007074:Immunoglobulin G; D014765:Viral Vaccines; D007371:Interferon-gamma
Nature. 2002 Jan 17;415(6869):331-5
11797011
Virology. 2006 Sep 30;353(2):324-32
16820184
Cancer Res. 2002 Oct 15;62(20):5792-9
12384540
Nat Med. 2003 Jun;9(6):729-35
12766765
Mol Genet Metab. 2003 Sep-Oct;80(1-2):148-58
14567964
Virology. 2003 Oct 25;315(2):345-52
14585337
Breast Cancer Res Treat. 2003 Dec;82(3):169-83
14703064
Clin Diagn Lab Immunol. 1999 Nov;6(6):953-8
10548592
J Virol. 2000 Jan;74(2):914-22
10623754
Vaccine. 2000 May 8;18(22):2426-34
10738100
J Gen Virol. 2000 Jul;81(Pt 7):1659-67
10859370
Virology. 2000 Dec 5;278(1):55-9
11112481
J Virol. 2001 Mar;75(6):2660-4
11222689
Infect Immun. 2001 Sep;69(9):5709-15
11500447
J Virol. 2001 Dec;75(23):11677-85
11689649
Cancer Res. 2001 Nov 1;61(21):7861-7
11691804
Am J Trop Med Hyg. 2001 Nov;65(5):420-6
11716093
J Gen Virol. 2002 Jan;83(Pt 1):75-80
11752703
Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):24-31
14740952
Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):48-60
14740955
Nature. 1977 Feb 24;265(5596):739-41
404559
Annu Rev Microbiol. 1990;44:649-88
2174669
J Clin Lab Anal. 1993;7(4):230-7
8395596
J Virol. 1997 Apr;71(4):3031-8
9060663
Virology. 1997 Dec 22;239(2):389-401
9434729
Clin Microbiol Rev. 1998 Jul;11(3):480-96
9665979
Lancet. 1998 Sep 19;352(9132):971-7
9752834
J Virol. 1998 Dec;72(12):10180-8
9811759
Scand J Immunol. 1999 Jun;49(6):595-610
10354371
J Virol. 2004 Dec;78(24):13819-28
15564490
Infect Immun. 2005 Sep;73(9):5978-87
16113318
Vaccine. 2006 Feb 27;24(9):1238-41
16213632
Methods Mol Med. 2006;127:171-97
16988455
Am J Trop Med Hyg. 2002 Mar;66(3):264-72
12139219