Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

被引：393

作者：

Barouch, Dan H. ^{[1
,2
]}

Liu, Jinyan ^{[1
]}

Li, Hualin ^{[1
]}

Maxfield, Lori F. ^{[1
]}

Abbink, Peter ^{[1
]}

Lynch, Diana M. ^{[1
]}

Iampietro, M. Justin ^{[1
]}

SanMiguel, Adam ^{[1
]}

Seaman, Michael S. ^{[1
]}

Ferrari, Guido ^{[3
]}

Forthal, Donald N. ^{[4
]}

Ourmanov, Ilnour ^{[5
]}

Hirsch, Vanessa M. ^{[5
]}

Carville, Angela ^{[6
]}

Mansfield, Keith G. ^{[6
]}

Stablein, Donald ^{[7
]}

Pau, Maria G. ^{[8
]}

Schuitemaker, Hanneke ^{[8
]}

Sadoff, Jerald C. ^{[8
]}

Billings, Erik A. ^{[9
]}

Rao, Mangala ^{[9
]}

Robb, Merlin L. ^{[9
]}

Kim, Jerome H. ^{[9
]}

Marovich, Mary A. ^{[9
]}

Goudsmit, Jaap ^{[8
]}

Michael, Nelson L. ^{[9
]}

机构：

[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA

[2] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA

[3] Duke Univ, Med Ctr, Durham, NC 27710 USA

[4] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA

[5] NIAID, Bethesda, MA 20892 USA

[6] New England Primate Res Ctr, Southborough, MA 01772 USA

[7] EMMES Corp, Rockville, MD 20850 USA

[8] Crucell Holland BV, NL-2301 CA Leiden, Netherlands

[9] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA

来源：

NATURE | 2012年 / 482卷 / 7383期

基金：

美国国家卫生研究院;

关键词：

CELLULAR IMMUNE-RESPONSES; LOW-DOSE CHALLENGE; INFECTION; ANTIBODIES; MACAQUES; VECTORS; MEMORY; BREADTH;

D O I：

10.1038/nature10766

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges(1-3). Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection(4,5) against repetitive, intrarectal SIVMAC251 challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.

引用

页码：89 / U115

页数：6

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