Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant.
We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV(SF162P4) following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1(SF162) gp140DeltaV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV(SF162P4) (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry.
Barnett
Susan W
SW
Novartis Vaccines and Diagnostics, 350 Massachusetts Avenue, Cambridge, MA 02139, USA. susan.barnett@novartis.com
Burke
Brian
B
Sun
Yide
Y
Kan
Elaine
E
Legg
Harold
H
Lian
Ying
Y
Bost
Kristen
K
Zhou
Fengmin
F
Goodsell
Amanda
A
Zur Megede
Jan
J
Polo
John
J
Donnelly
John
J
Ulmer
Jeffrey
J
Otten
Gillis R
GR
Miller
Christopher J
CJ
Vajdy
Michael
M
Srivastava
Indresh K
IK
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000524:Alphavirus / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D008251:Macaca; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D012093:Replicon; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C089950:MF59 oil emulsion; D011136:Polysorbates; D054299:env Gene Products, Human Immunodeficiency Virus; D013185:Squalene
Vaccine. 2009 Mar 23;27(14):1997-2015
19200450
Lancet. 2008 Nov 29;372(9653):1894-1905
19012957
AIDS Res Hum Retroviruses. 1998 Oct;14 Suppl 3:S299-309
9814958
AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):985-92
8827214
Vaccine. 2009 Dec 11;28(2):494-511
19833247
Dev Biol (Basel). 2000;104:181-5
11713818
Nat Med. 1997 Jun;3(6):651-8
9176492
Lancet. 2008 Nov 29;372(9653):1857-1858
19012958
J Exp Med. 2008 Jan 21;205(1):7-12
18195078
AIDS Res Hum Retroviruses. 1995 Mar;11(3):373-81
7598771
J Virol. 2003 Oct;77(20):11244-59
14512572
Trends Microbiol. 2008 Dec;16(12):605-11
18964016
Virology. 2008 Dec 20;382(2):217-25
18947849
Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4192-7
10759543
J Virol. 1996 Mar;70(3):1953-60
8627721
Curr HIV Res. 2007 Nov;5(6):594-607
18045116
Virology. 1998 Oct 25;250(2):293-301
9792840
J Virol. 2003 Oct;77(19):10394-403
12970424
J Virol. 2002 Mar;76(6):2835-47
11861851
Clin Vaccine Immunol. 2008 Apr;15(4):697-706
18287579
Nature. 2009 Jan 1;457(7225):87-91
18997770
Nat Med. 2009 Mar;15(3):293-9
19219024
J Virol. 2009 Jul;83(13):6508-21
19403685
AIDS Res Hum Retroviruses. 2008 Aug;24(8):1103-16
18620495
Virology. 2006 Jun 5;349(2):276-89
16527321
Science. 1992 Jan 24;255(5043):456-9
1531159
Immunol Lett. 2001 Nov 1;79(1-2):47-55
11595289
Curr Opin HIV AIDS. 2008 May;3(3):393-8
19372996
J Immunol. 2005 Feb 15;174(4):2185-9
15699150
Curr HIV Res. 2007 Nov;5(6):642-55
18045119
AIDS Res Hum Retroviruses. 2006 Oct;22(10):993-7
17067269
J Virol. 2005 Nov;79(21):13338-49
16227256
Vaccine. 2007 Jan 5;25(3):481-9
17052811
J Virol. 2004 Mar;78(5):2212-21
14963117
J Am Coll Nutr. 1995 Dec;14(6):656-61
8598428
AIDS Res Hum Retroviruses. 2006 Oct;22(10):1022-30
17067273
Virology. 2004 Mar 1;320(1):167-80
15003872
Virology. 2008 Mar 15;372(2):273-90
18061231
J Virol. 1999 Apr;73(4):3134-46
10074165
Vaccine. 2008 Dec 2;26(51):6592-601
18848857
N Engl J Med. 2009 Dec 3;361(23):2209-20
19843557
Lancet. 2008 Nov 29;372(9653):1881-1893
19012954
J Virol. 2009 May;83(9):4102-11
19224993
J Virol. 2009 Sep;83(18):9584-90
19553307
J Virol. 2006 Sep;80(18):9217-25
16940533
J Leukoc Biol. 2009 Oct;86(4):779-93
19597003
J Virol. 2005 Aug;79(16):10108-25
16051804
J Virol. 2005 Jun;79(11):7135-45
15890953
J Virol. 2001 Nov;75(22):10870-9
11602727
J Virol. 2010 Apr;84(8):3798-807
20130066
AIDS. 2008 Jan 30;22(3):339-48
18195560
PLoS Med. 2008 Aug 12;5(8):e173
18700814
Vaccine. 2007 Oct 16;25(42):7441-9
17870214
J Med Primatol. 2008 Dec;37 Suppl 2:13-23
19187427
Virology. 2006 Aug 15;352(1):131-44
21894641
J Virol. 2003 May;77(10):6087-92
12719603
Expert Rev Vaccines. 2008 Nov;7(9):1419-34
18980543
Nat Med. 2009 Aug;15(8):951-4
19525965
J Immunol. 2009 Mar 15;182(6):3718-27
19265150
Curr Protoc Immunol. 2005 Jan;Chapter 12:12.11.1-12.11.17
18432938