title: Lentiviral vector-based prime/boost vaccination against AIDS: pilot study shows protection against Simian immunodeficiency virus SIVmac251 challenge in macaques.
abstract: 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.
authors.affiliation: NRS URA 3015, Virologie Moléculaire et Vectorologie, Institut Pasteur, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Beignon
authors.forename: Karine
authors.initials: K
authors.lastname: Mollier
authors.forename: Christelle
authors.initials: C
authors.lastname: Liard
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coutant
authors.forename: Sandie
authors.initials: S
authors.lastname: Munier
authors.forename: Julie
authors.initials: J
authors.lastname: Rivière
authors.forename: Philippe
authors.initials: P
authors.lastname: Souque
authors.forename: Pierre
authors.initials: P
authors.lastname: Charneau
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag; D016282:Aspartic Acid Endopeptidases; C077164:SIV(mac) proteinase
references.citation: Cell. 2000 Apr 14;101(2):173-85
references.pmid: 10786833
references.citation: Vaccine. 2008 Jun 19;26(26):3312-21
references.pmid: 18486283
references.citation: Gene Ther. 2007 Jun;14(11):847-62
references.pmid: 17361214
references.citation: J Virol. 2007 Jan;81(2):539-47
references.pmid: 17079284
references.citation: Nat Med. 2007 Jan;13(1):46-53
references.pmid: 17173051
references.citation: Immunogenetics. 2009 May;61(5):327-39
references.pmid: 19337730
references.citation: Virology. 2007 Jun 5;362(2):304-13
references.pmid: 17292937
references.citation: J Virol. 2005 Dec;79(24):15547-55
references.pmid: 16306625
references.citation: PLoS Pathog. 2009 Jan;5(1):e1000272
references.pmid: 19165322
references.citation: Expert Rev Vaccines. 2008 Nov;7(9):1419-34
references.pmid: 18980543
references.citation: Nature. 2009 Jan 1;457(7225):87-91
references.pmid: 18997770
references.citation: J Virol. 2005 Jul;79(14):8878-85
references.pmid: 15994781
references.citation: J Exp Med. 2006 Jun 12;203(6):1533-41
references.pmid: 16735692
references.citation: J Virol. 2009 Jul;83(13):6508-21
references.pmid: 19403685
references.citation: Blood. 2007 Apr 1;109(7):2797-805
references.pmid: 17170119
references.citation: Lancet. 2008 Nov 29;372(9653):1894-1905
references.pmid: 19012957
references.citation: J Virol. 2004 Jul;78(14):7843-5
references.pmid: 15220461
references.citation: J Med Primatol. 2009 Feb;38(1):1-14
references.pmid: 19018947
references.citation: J Exp Med. 2008 Oct 27;205(11):2537-50
references.pmid: 18838548
references.citation: N Engl J Med. 1995 Jan 26;332(4):201-8
references.pmid: 7808485
references.citation: J Virol. 2001 Nov;75(22):10991-1001
references.pmid: 11602739
references.citation: Science. 1999 Feb 5;283(5403):857-60
references.pmid: 9933172
references.citation: J Exp Med. 2007 Sep 3;204(9):2171-85
references.pmid: 17724130
references.citation: Blood. 2008 Nov 1;112(9):3772-6
references.pmid: 18703703
references.citation: J Exp Med. 1999 Mar 15;189(6):991-8
references.pmid: 10075982
references.citation: Mol Ther. 2004 Oct;10(4):768-79
references.pmid: 15451461
references.citation: Mol Ther. 2007 Jun;15(6):1203-10
references.pmid: 17375069
references.citation: J Gen Virol. 2008 Sep;89(Pt 9):2240-2251
references.pmid: 18753233
references.citation: Science. 1998 Mar 27;279(5359):2103-6
references.pmid: 9516110
references.citation: J Virol. 2006 Jun;80(12):5875-85
references.pmid: 16731926
references.citation: Vaccine. 2008 Jan 24;26(4):532-45
references.pmid: 18093703
references.citation: J Gene Med. 2006 Mar;8(3):265-74
references.pmid: 16308885
references.citation: Immunity. 2006 May;24(5):643-56
references.pmid: 16713981
references.citation: J Gene Med. 2002 Jan-Feb;4(1):38-45
references.pmid: 11828386
references.citation: J Virol. 2005 Jul;79(13):8131-41
references.pmid: 15956558
references.citation: Lancet. 2008 Nov 29;372(9653):1881-1893
references.pmid: 19012954
references.citation: J Virol. 2005 Dec;79(24):15556-66
references.pmid: 16306626
references.citation: Viral Immunol. 2006 Winter;19(4):690-701
references.pmid: 17201664
references.citation: J Virol. 2007 Dec;81(24):13456-68
references.pmid: 17913797
references.citation: PLoS One. 2008;3(12):e3973
references.pmid: 19096527
references.citation: J Exp Med. 2008 Jan 21;205(1):7-12
references.pmid: 18195078
references.citation: Expert Opin Biol Ther. 2009 Jan;9(1):55-69
references.pmid: 19063693
references.citation: J Gen Virol. 2006 Jun;87(Pt 6):1625-1634
references.pmid: 16690927
references.citation: AIDS. 2007 Apr 23;21(7):889-91
references.pmid: 17415054
references.citation: Vaccine. 2001 May 14;19(25-26):3526-36
references.pmid: 11348720
references.citation: Mol Ther. 2006 Feb;13(2):310-9
references.pmid: 16275163
references.citation: J Med Primatol. 2004 Oct;33(5-6):251-61
references.pmid: 15525326
references.citation: J Virol. 2000 Mar;74(6):2628-35
references.pmid: 10684277
references.citation: J Virol. 2008 Apr;82(7):3166-80
references.pmid: 17989174
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6776-81
references.pmid: 17428922
references.citation: J Virol. 2009 Jun;83(12):6011-9
references.pmid: 19339351
references.citation: Science. 2006 Jun 9;312(5779):1530-3
references.pmid: 16763152
references.citation: Curr Opin Mol Ther. 2007 Oct;9(5):439-46
references.pmid: 17932808
references.citation: Blood. 2006 Jun 15;107(12):4781-9
references.pmid: 16467198
references.citation: J Virol. 2008 Apr;82(8):4135-48
references.pmid: 18272584
references.citation: J Med Primatol. 2001 Aug;30(4):207-14
references.pmid: 11555139
references.citation: J Virol. 2007 Jan;81(1):349-61
references.pmid: 17035320
references.citation: Cancer Res. 2006 Jan 15;66(2):1155-60
references.pmid: 16424053
references.citation: J Immunol. 2006 Jan 1;176(1):85-96
references.pmid: 16365399
references.citation: Cell. 2001 Sep 7;106(5):539-49
references.pmid: 11551502