Lentiviral vector-based prime/boost vaccination against AIDS: pilot study shows protection against Simian immunodeficiency virus SIVmac251 challenge in macaques.
AIDS vaccination has a pressing need for more potent vaccination vectors capable of eliciting strong, diversified, and long-lasting cellular immune responses against human immunodeficiency virus (HIV). Lentiviral vectors have demonstrated efficiency not only as gene delivery vehicles for gene therapy applications but also as vaccination tools. This is likely due to their ability to transduce nondividing cells, including dendritic cells, enabling sustained endogenous antigen presentation and thus the induction of high proportions of specific cytotoxic T cells and long-lasting memory T cells. We show in a first proof-of-concept pilot study that a prime/boost vaccination strategy using lentiviral vectors pseudotyped with a glycoprotein G from two non-cross-reactive vesicular stomatitis virus serotypes elicited robust and broad cellular immune responses against the vector-encoded antigen, simian immunodeficiency virus (SIV) GAG, in cynomolgus macaques. Vaccination conferred strong protection against a massive intrarectal challenge with SIVmac251, as evidenced both by the reduction of viremia at the peak of acute infection (a mean of over 2 log(10) fold reduction) and by the full preservation of the CD28(+) CD95(+) memory CD4(+) T cells during the acute phase, a strong correlate of protection against pathogenesis. Although vaccinees continued to display lower viremia than control macaques during the early chronic phase, these differences were not statistically significant by day 50 postchallenge. A not-optimized SIV GAG antigen was chosen to show the strong potential of the lentiviral vector system for vaccination. Given that a stronger protection can be anticipated from a modern HIV-1 antigen design, gene transfer vectors derived from HIV-1 appear as promising candidates for vaccination against HIV-1 infection.
Beignon
Anne-Sophie
AS
NRS URA 3015, Virologie Moléculaire et Vectorologie, Institut Pasteur, France.
Mollier
Karine
K
Liard
Christelle
C
Coutant
Frédéric
F
Munier
Sandie
S
Rivière
Julie
J
Souque
Philippe
P
Charneau
Pierre
P
D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000276:immunology; D008251:Macaca / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D008297:Male; D010865:Pilot Projects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D014766:Viremia
D016915:AIDS Vaccines; D015683:Gene Products, gag; D016282:Aspartic Acid Endopeptidases; C077164:SIV(mac) proteinase
Cell. 2000 Apr 14;101(2):173-85
10786833
Vaccine. 2008 Jun 19;26(26):3312-21
18486283
Gene Ther. 2007 Jun;14(11):847-62
17361214
J Virol. 2007 Jan;81(2):539-47
17079284
Nat Med. 2007 Jan;13(1):46-53
17173051
Immunogenetics. 2009 May;61(5):327-39
19337730
Virology. 2007 Jun 5;362(2):304-13
17292937
J Virol. 2005 Dec;79(24):15547-55
16306625
PLoS Pathog. 2009 Jan;5(1):e1000272
19165322
Expert Rev Vaccines. 2008 Nov;7(9):1419-34
18980543
Nature. 2009 Jan 1;457(7225):87-91
18997770
J Virol. 2005 Jul;79(14):8878-85
15994781
J Exp Med. 2006 Jun 12;203(6):1533-41
16735692
J Virol. 2009 Jul;83(13):6508-21
19403685
Blood. 2007 Apr 1;109(7):2797-805
17170119
Lancet. 2008 Nov 29;372(9653):1894-1905
19012957
J Virol. 2004 Jul;78(14):7843-5
15220461
J Med Primatol. 2009 Feb;38(1):1-14
19018947
J Exp Med. 2008 Oct 27;205(11):2537-50
18838548
N Engl J Med. 1995 Jan 26;332(4):201-8
7808485
J Virol. 2001 Nov;75(22):10991-1001
11602739
Science. 1999 Feb 5;283(5403):857-60
9933172
J Exp Med. 2007 Sep 3;204(9):2171-85
17724130
Blood. 2008 Nov 1;112(9):3772-6
18703703
J Exp Med. 1999 Mar 15;189(6):991-8
10075982
Mol Ther. 2004 Oct;10(4):768-79
15451461
Mol Ther. 2007 Jun;15(6):1203-10
17375069
J Gen Virol. 2008 Sep;89(Pt 9):2240-2251
18753233
Science. 1998 Mar 27;279(5359):2103-6
9516110
J Virol. 2006 Jun;80(12):5875-85
16731926
Vaccine. 2008 Jan 24;26(4):532-45
18093703
J Gene Med. 2006 Mar;8(3):265-74
16308885
Immunity. 2006 May;24(5):643-56
16713981
J Gene Med. 2002 Jan-Feb;4(1):38-45
11828386
J Virol. 2005 Jul;79(13):8131-41
15956558
Lancet. 2008 Nov 29;372(9653):1881-1893
19012954
J Virol. 2005 Dec;79(24):15556-66
16306626
Viral Immunol. 2006 Winter;19(4):690-701
17201664
J Virol. 2007 Dec;81(24):13456-68
17913797
PLoS One. 2008;3(12):e3973
19096527
J Exp Med. 2008 Jan 21;205(1):7-12
18195078
Expert Opin Biol Ther. 2009 Jan;9(1):55-69
19063693
J Gen Virol. 2006 Jun;87(Pt 6):1625-1634
16690927
AIDS. 2007 Apr 23;21(7):889-91
17415054
Vaccine. 2001 May 14;19(25-26):3526-36
11348720
Mol Ther. 2006 Feb;13(2):310-9
16275163
J Med Primatol. 2004 Oct;33(5-6):251-61
15525326
J Virol. 2000 Mar;74(6):2628-35
10684277
J Virol. 2008 Apr;82(7):3166-80
17989174
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6776-81
17428922
J Virol. 2009 Jun;83(12):6011-9
19339351
Science. 2006 Jun 9;312(5779):1530-3
16763152
Curr Opin Mol Ther. 2007 Oct;9(5):439-46
17932808
Blood. 2006 Jun 15;107(12):4781-9
16467198
J Virol. 2008 Apr;82(8):4135-48
18272584
J Med Primatol. 2001 Aug;30(4):207-14
11555139
J Virol. 2007 Jan;81(1):349-61
17035320
Cancer Res. 2006 Jan 15;66(2):1155-60
16424053
J Immunol. 2006 Jan 1;176(1):85-96
16365399
Cell. 2001 Sep 7;106(5):539-49
11551502