Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody

被引：318

作者：

Corti, Davide ^{[1
,2
]}

Misasi, John ^{[3
]}

Mulangu, Sabue ^{[3
]}

Stanley, Daphne A. ^{[3
]}

Kanekiyo, Masaru ^{[3
]}

Wollen, Suzanne ^{[4
]}

Ploquin, Aurelie ^{[3
]}

Doria-Rose, Nicole A. ^{[3
]}

Staupe, Ryan P. ^{[3
]}

Bailey, Michael ^{[3
]}

Shi, Wei ^{[3
]}

Choe, Misook ^{[3
]}

Marcus, Hadar ^{[3
]}

Thompson, Emily A. ^{[3
]}

Cagigi, Alberto ^{[3
]}

Silacci, Chiara ^{[1
]}

Fernandez-Rodriguez, Blanca ^{[1
]}

Perez, Laurent ^{[1
]}

Sallusto, Federica ^{[1
]}

Vanzetta, Fabrizia ^{[2
]}

Agatic, Gloria ^{[2
]}

Cameroni, Elisabetta ^{[2
]}

Kisalu, Neville ^{[3
,5
]}

Gordon, Ingelise ^{[3
]}

Ledgerwood, Julie E. ^{[3
]}

Mascola, John R. ^{[3
]}

Graham, Barney S. ^{[3
]}

Muyembe-Tamfun, Jean-Jacques ^{[5
]}

Trefry, John C. ^{[4
]}

Lanzavecchia, Antonio ^{[1
,6
]}

Sullivan, Nancy J. ^{[3
]}

机构：

[1] Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland

[2] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland

[3] NIAID, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA

[5] Natl Lab Publ Hlth, Natl Inst Biomed Res, BP 1197, Kinshasa, DEM REP CONGO

[6] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland

来源：

SCIENCE | 2016年 / 351卷 / 6279期

关键词：

MONOCLONAL-ANTIBODIES; OUTBREAK; MONKEYS; DISEASE; ZAIRE;

D O I：

10.1126/science.aad5224

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：

Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.

引用

页码：1339 / 1342

页数：4

共 19 条

[1] Ebola Virus Disease in West Africa - The First 9 Months of the Epidemic and Forward Projections [J].

Aylward, Bruce ;

Barboza, Philippe ;

Bawo, Luke ;

Bertherat, Eric ;

Bilivogui, Pepe ;

Blake, Isobel ;

Brennan, Rick ;

Briand, Sylvie ;

Chakauya, Jethro Magwati ;

Chitala, Kennedy ;

Conteh, Roland M. ;

Cori, Anne ;

Croisier, Alice ;

Dangou, Jean-Marie ;

Diallo, Boubacar ;

Donnelly, Christl A. ;

Dye, Christopher ;

Eckmanns, Tim ;

Ferguson, Neil M. ;

Formenty, Pierre ;

Fuhrer, Caroline ;

Fukuda, Keiji ;

Garske, Tini ;

Gasasira, Alex ;

Gbanyan, Stephen ;

Graaff, Peter ;

Heleze, Emmanuel ;

Jambai, Amara ;

Jombart, Thibaut ;

Kasolo, Francis ;

Kadiobo, Albert Mbule ;

Keita, Sakoba ;

Kertesz, Daniel ;

Kone, Moussa ;

Lane, Chris ;

Markoff, Jered ;

Massaquoi, Moses ;

Mills, Harriet ;

Mulba, John Mike ;

Musa, Emmanuel ;

Myhre, Joel ;

Nasidi, Abdusalam ;

Nilles, Eric ;

Nouvellet, Pierre ;

Nshimirimana, Deo ;

Nuttall, Isabelle ;

Nyenswah, Tolbert ;

Olu, Olushayo ;

Pendergast, Scott ;

Perea, William .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (16) :1481-1495

[2] Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys [J].

Barouch, Dan H. ;

Whitney, James B. ;

Moldt, Brian ;

Klein, Florian ;

Oliveira, Thiago Y. ;

Liu, Jinyan ;

Stephenson, Kathryn E. ;

Chang, Hui-Wen ;

Shekhar, Karthik ;

Gupta, Sanjana ;

Nkolola, Joseph P. ;

Seaman, Michael S. ;

Smith, Kaitlin M. ;

Borducchi, Erica N. ;

Cabral, Crystal ;

Smith, Jeffrey Y. ;

Blackmore, Stephen ;

Sanisetty, Srisowmya ;

Perry, James R. ;

Beck, Matthew ;

Lewis, Mark G. ;

Rinaldi, William ;

Chakraborty, Arup K. ;

Poignard, Pascal ;

Nussenzweig, Michel C. ;

Burton, Dennis R. .

NATURE, 2013, 503 (7475) :224-+

[3]

Burke J, 1978, B WORLD HEALTH ORGAN, V56, P271

[4] Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection [J].

Cote, Marceline ;

Misasi, John ;

Ren, Tao ;

Bruchez, Anna ;

Lee, Kyungae ;

Filone, Claire Marie ;

Hensley, Lisa ;

Li, Qi ;

Ory, Daniel ;

Chandran, Kartik ;

Cunningham, James .

NATURE, 2011, 477 (7364) :344-U122

[5] Institutional failure led to Ebola outbreak "spiralling out of control," says MSF [J].

Gulland, Anne .

BMJ-BRITISH MEDICAL JOURNAL, 2015, 350

[6] Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1 [J].

Hezareh, M ;

Hessell, AJ ;

Jensen, RC ;

van de Winkel, JGJ ;

Parren, PWHI .

JOURNAL OF VIROLOGY, 2001, 75 (24) :12161-12168

[7] Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor [J].

Lee, Jeffrey E. ;

Fusco, Marnie L. ;

Hessell, Ann J. ;

Oswald, Wendelien B. ;

Burton, Dennis R. ;

Saphire, Erica Ollmann .

NATURE, 2008, 454 (7201) :177-U27

[8] Ebola virus can be effectively neutralized by antibody produced in natural human infection [J].

Maruyama, T ;

Rodriguez, LL ;

Jahrling, PB ;

Sanchez, A ;

Khan, AS ;

Nichol, ST ;

Peters, CJ ;

Parren, PWHI ;

Burton, DR .

JOURNAL OF VIROLOGY, 1999, 73 (07) :6024-6030

[9] Structural and molecular basis for Ebola virus neutralization by protective human antibodies [J].

Misasi, John ;

Gilman, Morgan S. A. ;

Kanekiyo, Masaru ;

Gui, Miao ;

Cagigi, Alberto ;

Mulangu, Sabue ;

Corti, Davide ;

Ledgerwood, Julie E. ;

Lanzavecchia, Antonio ;

Cunningham, James ;

Muyembe-Tamfun, Jean Jacques ;

Baxa, Ulrich ;

Graham, Barney S. ;

Xiang, Ye ;

Sullivan, Nancy J. ;

McLellan, Jason S. .

SCIENCE, 2016, 351 (6279) :1343-1346

[10] Structures of protective antibodies reveal sites of vulnerability on Ebola virus [J].

Murin, Charles D. ;

Fusco, Marnie L. ;

Bornholdt, Zachary A. ;

Qiu, Xiangguo ;

Olinger, Gene G. ;

Zeitlin, Larry ;

Kobinger, Gary P. ;

Ward, Andrew B. ;

Saphire, Erica Ollmann .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (48) :17182-17187

← 1 2 →