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

共 31 条

[21] Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies [J].

Mascola, JR ;

Stiegler, G ;

VanCott, TC ;

Katinger, H ;

Carpenter, CB ;

Hanson, CE ;

Beary, H ;

Hayes, D ;

Frankel, SS ;

Birx, DL ;

Lewis, MG .

NATURE MEDICINE, 2000, 6 (02) :207-210

[22] Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection [J].

Mattapallil, JJ ;

Douek, DC ;

Hill, B ;

Nishimura, Y ;

Martin, M ;

Roederer, M .

NATURE, 2005, 434 (7037) :1093-1097

[23] Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus [J].

Miller, CJ ;

Li, QS ;

Abel, K ;

Kim, EY ;

Ma, ZM ;

Wietgrefe, S ;

La Franco-Scheuch, L ;

Compton, L ;

Duan, LJ ;

Shore, MD ;

Zupancic, M ;

Busch, M ;

Carlis, J ;

Wolinksy, S ;

Haase, AT .

JOURNAL OF VIROLOGY, 2005, 79 (14) :9217-9227

[24] Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo [J].

Moldt, Brian ;

Rakasz, Eva G. ;

Schultz, Niccole ;

Chan-Hui, Po-Ying ;

Swiderek, Kristine ;

Weisgrau, Kimberly L. ;

Piaskowski, Shari M. ;

Bergman, Zachary ;

Watkins, David I. ;

Poignard, Pascal ;

Burton, Dennis R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (46) :18921-18925

[25] Fast integration of heterogeneous data sources for predicting gene function with limited annotation [J].

Mostafavi, Sara ;

Morris, Quaid .

BIOINFORMATICS, 2010, 26 (14) :1759-1765

[26] GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function [J].

Mostafavi, Sara ;

Ray, Debajyoti ;

Warde-Farley, David ;

Grouios, Chris ;

Morris, Quaid .

GENOME BIOLOGY, 2008, 9 (Suppl 1)

[27] A diverse range of gene products are effectors of the type I interferon antiviral response [J].

Schoggins, John W. ;

Wilson, Sam J. ;

Panis, Maryline ;

Murphy, Mary Y. ;

Jones, Christopher T. ;

Bieniasz, Paul ;

Rice, Charles M. .

NATURE, 2011, 472 (7344) :481-U545

[28] Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques [J].

Shingai, Masashi ;

Donau, Olivia K. ;

Plishka, Ronald J. ;

Buckler-White, Alicia ;

Mascola, John R. ;

Nabel, Gary J. ;

Nason, Martha C. ;

Montefiori, David ;

Moldt, Brian ;

Poignard, Pascal ;

Diskin, Ron ;

Bjorkman, Pamela J. ;

Eckhaus, Michael A. ;

Klein, Florian ;

Mouquet, Hugo ;

Lorenzi, Julio Cesar Cetrulo ;

Gazumyan, Anna ;

Burton, Dennis R. ;

Nussenzweig, Michel C. ;

Martin, Malcolm A. ;

Nishimura, Yoshiaki .

JOURNAL OF EXPERIMENTAL MEDICINE, 2014, 211 (10) :2061-2074

[29] Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles [J].

Subramanian, A ;

Tamayo, P ;

Mootha, VK ;

Mukherjee, S ;

Ebert, BL ;

Gillette, MA ;

Paulovich, A ;

Pomeroy, SL ;

Golub, TR ;

Lander, ES ;

Mesirov, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15545-15550

[30]

Veazey RS, 2003, NAT MED, V9, P343, DOI 10.1038/nm833

← 1 2 3 4 →