Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus

被引：125

作者：

Liu, Jinyan ^{[1
]}

Ghneim, Khader ^{[2
]}

Sok, Devin ^{[3
]}

Bosche, William J. ^{[4
]}

Li, Yuan ^{[4
]}

Chipriano, Elizabeth ^{[4
]}

Berkemeier, Brian ^{[4
]}

Oswald, Kelli ^{[4
]}

Borducchi, Erica ^{[1
]}

Cabral, Crystal ^{[1
]}

Peter, Lauren ^{[1
]}

Brinkman, Amanda ^{[1
]}

Shetty, Mayuri ^{[1
]}

Jimenez, Jessica ^{[1
]}

Mondesir, Jade ^{[1
]}

Lee, Benjamin ^{[1
]}

Giglio, Patricia ^{[1
]}

Chandrashekar, Abishek ^{[1
]}

Abbink, Peter ^{[1
]}

Colantonio, Arnaud ^{[5
]}

Gittens, Courtney ^{[6
]}

Baker, Chantelle ^{[6
]}

Wagner, Wendeline ^{[6
]}

Lewis, Mark G. ^{[6
]}

Li, Wenjun ^{[7
]}

Sekaly, Rafick-Pierre ^{[2
]}

Lifson, Jeffrey D. ^{[4
]}

Burton, Dennis R. ^{[3
,8
]}

Barouch, Dan H. ^{[1
,8
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[2] Case Western Reserve Univ, Cleveland, OH 44106 USA

[3] Scripps Res Inst, La Jolla, CA 92037 USA

[4] Frederick Natl Lab, AIDS & Canc Virus Program, Leidos Biomed Res, Frederick, MD 21702 USA

[5] Harvard Med Sch, Boston, MA 02115 USA

[6] Bioqual, Rockville, MD 20852 USA

[7] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA

[8] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA

来源：

SCIENCE | 2016年 / 353卷 / 6303期

基金：

美国国家卫生研究院;

关键词：

SIMIAN IMMUNODEFICIENCY VIRUS; PREDICTING GENE-FUNCTION; CD4(+) T-CELLS; RHESUS-MONKEYS; MONOCLONAL-ANTIBODIES; SIV INFECTION; NEUTRALIZING ANTIBODIES; VAGINAL TRANSMISSION; PASSIVE TRANSFER; IN-VIVO;

D O I：

10.1126/science.aag0491

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：

HIV-1-specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception of virus and the mechanism of antibody-mediated protection remain unclear. We administered a fully protective dose of the bNAb PGT121 to rhesus monkeys and challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels of viral RNA and viral DNA in distal tissues for seven days following challenge. Viral RNA-positive tissues showed transcriptomic changes indicative of innate immune activation, and cells from these tissues initiated infection after adoptive transfer into naive hosts. These data demonstrate that bNAb-mediated protection against a mucosal virus challenge can involve clearance of infectious virus in distal tissues.

引用

页码：1045 / 1049

页数：5

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