Successful Treatment of Ebola Virus-Infected Cynomolgus Macaques with Monoclonal Antibodies

被引:239
作者
Qiu, Xiangguo [1 ]
Audet, Jonathan [2 ]
Wong, Gary [2 ]
Pillet, Stephane [1 ]
Bello, Alexander [2 ]
Cabral, Teresa [1 ]
Strong, Jim E. [1 ]
Plummer, Frank [1 ]
Corbett, Cindy R. [1 ,2 ,3 ]
Alimonti, Judie B. [1 ,2 ]
Kobinger, Gary P. [1 ,2 ,3 ]
机构
[1] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada
[2] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada
[3] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0T5, Canada
关键词
ACTIVATED PROTEIN-C; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; ZAIRE-EBOLAVIRUS; MOUSE MODEL; VACCINE; MONKEYS; PROPHYLAXIS; IMMUNOGLOBULIN;
D O I
10.1126/scitranslmed.3003876
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ebola virus (EBOV) is considered one of the most aggressive infectious agents and is capable of causing death in humans and nonhuman primates (NHPs) within days of exposure. Recent strategies have succeeded in preventing acquisition of infection in NHPs after treatment; however, these strategies are only successful when administered before or minutes after infection. The present work shows that a combination of three neutralizing monoclonal antibodies (mAbs) directed against the Ebola envelope glycoprotein (GP) resulted in complete survival (four of four cynomolgus macaques) with no apparent side effects when three doses were administered 3 days apart beginning at 24 hours after a lethal challenge with EBOV. The same treatment initiated 48 hours after lethal challenge with EBOV resulted in two of four cynomolgus macaques fully recovering. The survivors demonstrated an EBOV-GP-specific humoral and cell-mediated immune response. These data highlight the important role of antibodies to control EBOV replication in vivo, and support the use of mAbs against a severe filovirus infection.
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页数:12
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共 37 条
  • [1] Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients
    Baize, S
    Leroy, EM
    Georges-Courbot, MC
    Capron, M
    Lansoud-Soukate, J
    Debré, P
    Fisher-Hoch, SP
    McCormick, JB
    McCormick, JB
    Georges, AJ
    [J]. NATURE MEDICINE, 1999, 5 (04) : 423 - 426
  • [2] Disease modeling for Ebola and Marburg viruses
    Bente, Dennis
    Gren, Jason
    Strong, James E.
    Feldmann, Heinz
    [J]. DISEASE MODELS & MECHANISMS, 2009, 2 (1-2) : 12 - 17
  • [3] Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis
    Bernard, GR
    Ely, EW
    Wright, TJ
    Fraiz, J
    Stasek, JE
    Russell, JA
    Mayers, I
    Rosenfeld, BA
    Morris, PE
    Yan, SB
    Helterbrand, JD
    [J]. CRITICAL CARE MEDICINE, 2001, 29 (11) : 2051 - 2059
  • [4] Borisevich IV, 1995, VOP VIRUSOL+, V40, P270
  • [5] A Neutralizing Human Monoclonal Antibody Protects African Green Monkeys from Hendra Virus Challenge
    Bossart, Katharine N.
    Geisbert, Thomas W.
    Feldmann, Heinz
    Zhu, Zhongyu
    Feldmann, Friederike
    Geisbert, Joan B.
    Yan, Lianying
    Feng, Yan-Ru
    Brining, Doug
    Scott, Dana
    Wang, Yanping
    Dimitrov, Antony S.
    Callison, Julie
    Chan, Yee-Peng
    Hickey, Andrew C.
    Dimitrov, Dimiter S.
    Broder, Christopher C.
    Rockx, Barry
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (105)
  • [6] EBOLA HEMORRHAGIC-FEVER - EXPERIMENTAL-INFECTION OF MONKEYS
    BOWEN, ETW
    PLATT, GS
    SIMPSON, DIH
    MCARDELL, LB
    RAYMOND, RT
    [J]. TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1978, 72 (02) : 188 - 191
  • [7] Lymphocyte death in a mouse model of Ebola virus infection
    Bradfute, Steven B.
    Braun, Denise R.
    Shamblin, Joshua D.
    Geisbert, Joan B.
    Paragas, Jason
    Garrison, Aura
    Hensley, Lisa E.
    Geisbert, Thomas W.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2007, 196 : S296 - S304
  • [8] Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease
    Dye, John M.
    Herbert, Andrew S.
    Kuehne, Ana I.
    Barth, James F.
    Muhammad, Majidat A.
    Zak, Samantha E.
    Ortiz, Ramon A.
    Prugar, Laura I.
    Pratt, William D.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (13) : 5034 - 5039
  • [9] In vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein
    Ebihara, Hideki
    Theriault, Steven
    Neumann, Gabriele
    Alimonti, Judie B.
    Geisbert, Joan B.
    Hensley, Lisa E.
    Groseth, Allison
    Jones, Steven M.
    Geisbert, Thomas W.
    Kawaoka, Yoshihiro
    Feldmann, Heinz
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2007, 196 : S313 - S322
  • [10] Effective post-exposure treatment of Ebola infection
    Feldmann, Heinz
    Jones, Steven M.
    Daddario-DiCaprio, Kathleen M.
    Geisbert, Joan B.
    Stroher, Ute
    Grolla, Allen
    Bray, Mike
    Fritz, Elizabeth A.
    Fernando, Lisa
    Feldmann, Friederike
    Hensley, Lisa E.
    Geisbert, Thomas W.
    [J]. PLOS PATHOGENS, 2007, 3 (01) : 54 - 61