Prime-boost vaccination using chemokine-fused gp120 DNA and HIV envelope peptides activates both immediate and long-term memory cellular responses in rhesus macaques.
HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFgamma ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.
Qin
Hong
H
Department of Lymphoma and Myeloma, M. D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
Nehete
Pramod N
PN
He
Hong
H
Nehete
Bharti
B
Buchl
Stephanie
S
Cha
Soung-Chul
SC
Sastry
Jagannadha K
JK
Kwak
Larry W
LW
D000818:Animals; D054410:Chemokine CCL7 / Q000276:immunology*; D004247:DNA; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods*; D007156:Immunologic Memory / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014611:Vaccination / Q000379:methods*
D054410:Chemokine CCL7; D015699:HIV Envelope Protein gp120; D010455:Peptides; D011993:Recombinant Fusion Proteins; D004247:DNA
J Infect Dis. 2006 Dec 15;194(12):1638-49
17109335
FEBS Lett. 1987 Aug 31;221(1):18-22
3305075
J Virol. 2006 Feb;80(4):1645-52
16439521
J Virol. 2003 Nov;77(21):11563-77
14557642
J Virol. 2002 Nov;76(22):11484-90
12388710
AIDS Res Hum Retroviruses. 1993 Mar;9(3):235-40
8471313
Science. 2002 Nov 1;298(5595):1025-9
12411706
Blood. 1988 Dec;72(6):2070-3
3264198
Blood. 2006 Jun 15;107(12):4597-605
16514063
Vaccine. 2004 Dec 9;23(4):555-65
15530705
J Immunol Methods. 2004 May;288(1-2):61-79
15183086
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251-5
2444978
N Engl J Med. 1997 Oct 30;337(18):1267-74
9345075
Vaccine. 2007 Dec 17;25(52):8687-701
18063450
Blood. 2002 Aug 15;100(4):1153-9
12149191
Science. 1999 Feb 5;283(5403):857-60
9933172
Vaccine. 2005 Mar 18;23(17-18):2154-9
15755586
J Intern Med. 2007 Jul;262(1):44-58
17598814
J Immunol. 2001 Dec 1;167(11):6644-53
11714836
Blood. 2009 Nov 5;114(19):4142-9
19749091
Viral Immunol. 1998;11(3):147-58
9918406
Clin Immunol Immunopathol. 1997 Mar;82(3):230-42
9073546
Nature. 1986 Nov 6-12;324(6092):70-3
3024009
Nat Biotechnol. 1999 Mar;17(3):253-8
10096292