Long-lasting humoral and cellular immune responses and mucosal dissemination after intramuscular DNA immunization.
Naïve Indian rhesus macaques were immunized with a mixture of optimized plasmid DNAs expressing several SIV antigens using in vivo electroporation via the intramuscular route. The animals were monitored for the development of SIV-specific systemic (blood) and mucosal (bronchoalveolar lavage) cellular and humoral immune responses. The immune responses were of great magnitude, broad (Gag, Pol, Nef, Tat and Vif), long-lasting (up to 90 weeks post third vaccination) and were boosted with each subsequent immunization, even after an extended 90-week rest period. The SIV-specific cellular immune responses were consistently more abundant in bronchoalveolar lavage (BAL) than in blood, and were characterized as predominantly effector memory CD4(+) and CD8(+) T cells in BAL and as both central and effector memory T cells in blood. SIV-specific T cells containing Granzyme B were readily detected in both blood and BAL, suggesting the presence of effector cells with cytolytic potential. DNA vaccination also elicited long-lasting systemic and mucosal humoral immune responses, including the induction of Gag-specific IgA. The combination of optimized DNA vectors and improved intramuscular delivery by in vivo electroporation has the potential to elicit both cellular and humoral responses and dissemination to the periphery, and thus to improve DNA immunization efficacy.
Patel
Vainav
V
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Building 535, Room 206, Frederick, MD 21702-1201, USA.
Valentin
Antonio
A
Kulkarni
Viraj
V
Rosati
Margherita
M
Bergamaschi
Cristina
C
Jalah
Rashmi
R
Alicea
Candido
C
Minang
Jacob T
JT
Trivett
Matthew T
MT
Ohlen
Claes
C
Zhao
Jun
J
Robert-Guroff
Marjorie
M
Khan
Amir S
AS
Draghia-Akli
Ruxandra
R
Felber
Barbara K
BK
Pavlakis
George N
GN
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D000918:Antibody Specificity; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000097:blood; D016503:Drug Delivery Systems; D018274:Electroporation; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D015683:Gene Products, gag; D007070:Immunoglobulin A; D018449:SAIDS Vaccines; D019444:Vaccines, DNA
Nat Rev Genet. 2008 Oct;9(10):776-88
18781156
Immunity. 2004 Mar;20(3):247-53
15030769
J Immunol. 2008 Sep 15;181(6):4188-98
18768876
J Virol. 2000 Aug;74(16):7485-95
10906202
Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15831-6
19717425
J Gen Virol. 2008 Feb;89(Pt 2):540-5533
18198386
Annu Rev Immunol. 2006;24:681-704
16551263
J Immunol. 2001 May 1;166(9):5473-9
11313385
Blood. 2006 Apr 15;107(8):3258-64
16373659
J Virol. 1994 May;68(5):2986-93
8151769
Nat Med. 2009 Mar;15(3):293-9
19219024
J Immunol. 2004 Mar 15;172(6):3745-57
15004179
Nat Med. 2001 Dec;7(12):1320-6
11726972
PLoS One. 2010 Jan 25;5(1):e8617
20111582
Tuberculosis (Edinb). 2007 Aug;87 Suppl 1:S35-44
17652028
Vaccine. 2008 May 23;26(22):2788-95
18440674
J Gen Virol. 2004 Apr;85(Pt 4):911-919
15039533
J Immunol. 2002 Jan 1;168(1):29-43
11751943
J Immunol. 2010 Jan 1;184(1):315-26
19949091
J Virol. 2002 Nov;76(22):11484-90
12388710
Vaccine. 2008 Feb 20;26(8):1098-110
18243434
J Virol. 2002 Nov;76(22):11659-76
12388726
Clin Vaccine Immunol. 2008 Jun;15(6):986-94
18400976
J Med Primatol. 2005 Oct;34(5-6):262-70
16128921
Curr Gene Ther. 2006 Apr;6(2):243-73
16611045
Nat Rev Immunol. 2006 Feb;6(2):148-58
16491139
J Virol. 2002 Apr;76(7):3309-17
11884556
Vaccine. 2007 Dec 17;25(52):8687-701
18063450
Vaccine. 2008 Jun 13;26(25):3112-20
18430495
Vaccine. 2003 Jan 30;21(7-8):629-37
12531331
Blood. 2002 Aug 15;100(4):1153-9
12149191
Nat Biotechnol. 1998 Sep;16(9):867-70
9743122
Vaccine. 2006 May 22;24(21):4677-87
16288822
J Infect Dis. 1999 Oct;180(4):1351-5
10479171
Vaccine. 2007 Oct 16;25(42):7470-9
17854955
Virology. 2006 Oct 25;354(2):299-315
16904153
J Virol. 1992 Jan;66(1):150-9
1727477
J Virol. 2003 Feb;77(4):2400-9
12551977
Vaccine. 2007 May 16;25(20):4085-92
17391815
Vaccine. 2004 Jun 23;22(19):2489-93
15193413
J Immunol. 2008 Jun 15;180(12):7969-79
18523260
Virology. 2000 Mar 1;268(1):94-103
10683331
J Virol. 1992 Dec;66(12):7176-82
1433510
J Clin Invest. 2006 Jun;116(6):1514-24
16691294
J Virol. 2006 Jun;80(12):5875-85
16731926
J Immunol. 2008 Oct 15;181(8):5618-26
18832720
J Virol. 2007 May;81(10):5257-69
17329330
Vaccine. 2007 Nov 19;25(47):8021-35
17935840
J Virol. 2005 Jul;79(13):8480-92
15956591
J Immunol. 2008 May 1;180(9):6159-67
18424737
Gene Ther. 1999 Apr;6(4):508-14
10476210
AIDS Res Hum Retroviruses. 2004 Aug;20(8):846-59
15320989
Gene Ther. 2004 Apr;11(8):711-21
14724672
Virology. 2007 Oct 10;367(1):156-67
17590405
J Virol. 2007 Feb;81(4):1972-9
17135321
Vaccine. 2003 Oct 1;21(27-30):4153-66
14505895
J Allergy Clin Immunol. 2008 Jul;122(1):3-9; quiz 10-1
18468671
Vaccine. 2007 Mar 8;25(12):2187-93
17229501
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6417-22
10339602
AIDS Rev. 2008 Jan-Mar;10(1):36-46
18385779
Vaccine. 2006 May 22;24(21):4503-9
16181711
Viral Immunol. 2005;18(1):236-43
15802969
Virology. 2004 Jun 1;323(2):220-32
15193918
J Infect Dis. 2006 Dec 15;194(12):1650-60
17109336
Blood. 2006 Jun 15;107(12):4781-9
16467198
Vaccine. 2008 Jan 10;26(2):215-23
18055072
J Immunol. 2000 May 1;164(9):4635-40
10779767
J Virol. 2006 Apr;80(8):3732-42
16571790
J Virol. 2008 Jul;82(13):6458-69
18448544
J Acquir Immune Defic Syndr. 2007 Apr 15;44(5):601-5
17325604
Immunol Lett. 2001 Nov 1;79(1-2):57-61
11595290
Virology. 2008 Nov 10;381(1):106-15
18793787
AIDS Res Hum Retroviruses. 2004 Apr;20(4):425-34
15157361
J Virol. 1997 Jul;71(7):4892-903
9188551
J Virol. 2000 Nov;74(22):10514-22
11044096
Vaccine. 2007 Nov 7;25(45):7737-42
17920731
J Virol. 2009 Jan;83(2):791-801
18971271
Vaccine. 2008 Sep 19;26(40):5223-9
18468743
Expert Rev Vaccines. 2007 Apr;6(2):203-12
17408370