Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody.

Abstract:

:Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe and often fatal disease in pigs and humans. There are currently no vaccines or treatments approved for human use. Studies in small-animal models of NiV infection suggest that antibody therapy may be a promising treatment. However, most studies have assessed treatment at times shortly after virus exposure before animals show signs of disease. We assessed the efficacy of a fully human monoclonal antibody, m102.4, at several time points after virus exposure including at the onset of clinical illness in a uniformly lethal nonhuman primate model of NiV disease. Sixteen African green monkeys (AGMs) were challenged intratracheally with a lethal dose of NiV, and 12 animals were infused twice with m102.4 (15 mg/kg) beginning at either 1, 3, or 5 days after virus challenge and again about 2 days later. The presence of viral RNA, infectious virus, and/or NiV-specific immune responses demonstrated that all subjects were infected after challenge. All 12 AGMs that received m102.4 survived infection, whereas the untreated control subjects succumbed to disease between days 8 and 10 after infection. AGMs in the day 5 treatment group exhibited clinical signs of disease, but all animals recovered by day 16. These results represent the successful therapeutic in vivo efficacy by an investigational drug against NiV in a nonhuman primate and highlight the potential impact that a monoclonal antibody can have on a highly pathogenic zoonotic human disease.

journal_name

Sci Transl Med

authors

Geisbert TW,Mire CE,Geisbert JB,Chan YP,Agans KN,Feldmann F,Fenton KA,Zhu Z,Dimitrov DS,Scott DP,Bossart KN,Feldmann H,Broder CC

doi

10.1126/scitranslmed.3008929

subject

Has Abstract

pub_date

2014-06-25 00:00:00

pages

242ra82

issue

242

eissn

1946-6234

issn

1946-6242

pii

6/242/242ra82

journal_volume

6

pub_type

杂志文章
  • Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation.

    abstract::Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kin...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaw3521

    authors: Tang AT,Sullivan KR,Hong CC,Goddard LM,Mahadevan A,Ren A,Pardo H,Peiper A,Griffin E,Tanes C,Mattei LM,Yang J,Li L,Mericko-Ishizuka P,Shen L,Hobson N,Girard R,Lightle R,Moore T,Shenkar R,Polster SP,Roedel CJ,Li

    更新日期:2019-11-27 00:00:00

  • Forty-year journey of angiogenesis translational research.

    abstract::Forty years ago, Judah Folkman predicted that tumor growth is dependent on angiogenesis and that inhibiting this process might be a new strategy for cancer therapy. This hypothesis formed the foundation of a new field of research that represents an excellent example of how a groundbreaking scientific discovery can be ...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3003149

    authors: Cao Y,Arbiser J,D'Amato RJ,D'Amore PA,Ingber DE,Kerbel R,Klagsbrun M,Lim S,Moses MA,Zetter B,Dvorak H,Langer R

    更新日期:2011-12-21 00:00:00

  • Estimating cholera incidence with cross-sectional serology.

    abstract::The development of new approaches to cholera control relies on an accurate understanding of cholera epidemiology. However, most information on cholera incidence lacks laboratory confirmation and instead relies on surveillance systems reporting medically attended acute watery diarrhea. If recent infections could be ide...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aau6242

    authors: Azman AS,Lessler J,Luquero FJ,Bhuiyan TR,Khan AI,Chowdhury F,Kabir A,Gurwith M,Weil AA,Harris JB,Calderwood SB,Ryan ET,Qadri F,Leung DT

    更新日期:2019-02-20 00:00:00

  • Complexity in common diseases: big biology for all.

    abstract::The Commentary of Mills and Sykes in Science Translational Medicine presented their thesis on the advent of high-throughput technologies and the dangers they may represent for the future of biomedical research. In response, we argue that true progress on the diagnosis and treatment of common human diseases will requir...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.3000882

    authors: Lamb JR,Gibson NW

    更新日期:2010-03-31 00:00:00

  • Fresh approaches to anti-infective therapies.

    abstract::If discovery of new antibiotics continues to falter while resistance to drugs in clinical use continues to spread, society's medicine chest will soon lack effective treatments for many infections. Heritable antibiotic resistance emerges in bacteria from nonheritable resistance, also called phenotypic tolerance. This w...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3003081

    authors: Nathan C

    更新日期:2012-06-27 00:00:00

  • Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.

    abstract::Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aal2774

    authors: Hoyle NP,Seinkmane E,Putker M,Feeney KA,Krogager TP,Chesham JE,Bray LK,Thomas JM,Dunn K,Blaikley J,O'Neill JS

    更新日期:2017-11-08 00:00:00

  • Designing a public square for research computing.

    abstract::A set of principles is proposed for sponsors and developers of research computing applications that can increase the likelihood of successful adoption by researchers. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3004032

    authors: Masys DR,Harris PA,Fearn PA,Kohane IS

    更新日期:2012-08-29 00:00:00

  • In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma.

    abstract::Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aat5857

    authors: Galanzha EI,Menyaev YA,Yadem AC,Sarimollaoglu M,Juratli MA,Nedosekin DA,Foster SR,Jamshidi-Parsian A,Siegel ER,Makhoul I,Hutchins LF,Suen JY,Zharov VP

    更新日期:2019-06-12 00:00:00

  • Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase.

    abstract::Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction a...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aal1669

    authors: Ziegler SG,Ferreira CR,MacFarlane EG,Riddle RC,Tomlinson RE,Chew EY,Martin L,Ma CT,Sergienko E,Pinkerton AB,Millán JL,Gahl WA,Dietz HC

    更新日期:2017-06-07 00:00:00

  • Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system.

    abstract::Optogenetics offers promise for dissecting the complex neural circuits of the spinal cord and peripheral nervous system and has therapeutic potential for addressing unmet clinical needs. Much progress has been made to enable optogenetic control in normal and disease states, both in proof-of-concept and mechanistic stu...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aad7577

    authors: Montgomery KL,Iyer SM,Christensen AJ,Deisseroth K,Delp SL

    更新日期:2016-05-04 00:00:00

  • Impact of guidance documents on translational large animal studies of cartilage repair.

    abstract::Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aac7019

    authors: Pfeifer CG,Fisher MB,Carey JL,Mauck RL

    更新日期:2015-10-21 00:00:00

  • Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody.

    abstract::As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aai8711

    authors: Mire CE,Geisbert JB,Borisevich V,Fenton KA,Agans KN,Flyak AI,Deer DJ,Steinkellner H,Bohorov O,Bohorova N,Goodman C,Hiatt A,Kim DH,Pauly MH,Velasco J,Whaley KJ,Crowe JE Jr,Zeitlin L,Geisbert TW

    更新日期:2017-04-05 00:00:00

  • Changing models of biomedical research.

    abstract::Thanks to the revolutions in information technology, human "-omics" research, and intricate medical device development, academic health centers (AHCs) now have an unparalleled potential to become translational engines that both generate basic science advances and then translate them into human studies and, ultimately,...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000124

    authors: Crowley WF Jr,Gusella JF

    更新日期:2009-10-07 00:00:00

  • Turning back the clock.

    abstract::Increased DNA breaks in aging skeletal muscle activate the DNA-PK pathway, whereas blocking this pathway improves mitochondrial density, physical fitness, body weight, and insulin resistance in mice. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aan4290

    authors: Shoemaker AH

    更新日期:2017-05-17 00:00:00

  • Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.

    abstract::Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whe...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008918

    authors: Kvistborg P,Philips D,Kelderman S,Hageman L,Ottensmeier C,Joseph-Pietras D,Welters MJ,van der Burg S,Kapiteijn E,Michielin O,Romano E,Linnemann C,Speiser D,Blank C,Haanen JB,Schumacher TN

    更新日期:2014-09-17 00:00:00

  • Electronic consent channels: preserving patient privacy without handcuffing researchers.

    abstract::Advances in health information technology and electronic medical records have the tremendous potential to accelerate translational and clinical research. However, privacy concerns threaten to be a rate-limiting factor. By recognizing and responding to patient privacy concerns, policy-makers, researchers, and informati...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002037

    authors: Shelton RH

    更新日期:2011-02-09 00:00:00

  • Epidermal electronics for noninvasive, wireless, quantitative assessment of ventricular shunt function in patients with hydrocephalus.

    abstract::Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current...

    journal_title:Science translational medicine

    pub_type: 临床试验,杂志文章

    doi:10.1126/scitranslmed.aat8437

    authors: Krishnan SR,Ray TR,Ayer AB,Ma Y,Gutruf P,Lee K,Lee JY,Wei C,Feng X,Ng B,Abecassis ZA,Murthy N,Stankiewicz I,Freudman J,Stillman J,Kim N,Young G,Goudeseune C,Ciraldo J,Tate M,Huang Y,Potts M,Rogers JA

    更新日期:2018-10-31 00:00:00

  • Working stiff: how obesity boosts cancer risk.

    abstract::Obesity promotes breast cancer by enhancing the stiffness of breast adipose tissue through changes in the extracellular matrix (Seo et al., this issue). ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aac9446

    authors: Arendt LM,Kuperwasser C

    更新日期:2015-08-19 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract::Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000522

    authors: Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期:2010-04-21 00:00:00

  • Stem cells, dot-com.

    abstract::Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of s...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3004030

    authors: Liang BA,Mackey TK

    更新日期:2012-09-12 00:00:00

  • Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model.

    abstract::Down syndrome (DS) is among the most frequent genetic causes of intellectual disability, and ameliorating this deficit is a major goal in support of people with trisomy 21. The Ts65Dn mouse recapitulates some major brain structural and behavioral phenotypes of DS, including reduced size and cellularity of the cerebell...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3005983

    authors: Das I,Park JM,Shin JH,Jeon SK,Lorenzi H,Linden DJ,Worley PF,Reeves RH

    更新日期:2013-09-04 00:00:00

  • Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression.

    abstract::Lung cancer is more deadly than colon, breast, and prostate cancers combined, and treatment improvements have failed to improve prognosis significantly. Here, we identify a critical mediator of lung cancer progression, Rac1b, a tumor-associated protein with cell-transforming properties that are linked to the matrix me...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3004062

    authors: Stallings-Mann ML,Waldmann J,Zhang Y,Miller E,Gauthier ML,Visscher DW,Downey GP,Radisky ES,Fields AP,Radisky DC

    更新日期:2012-07-11 00:00:00

  • Comment on "ALK is a therapeutic target for lethal sepsis".

    abstract::Physiologically relevant ALK (anaplastic lymphoma kinase) expression was not detected in human and mouse monocytes and macrophages, suggesting that the effects of bioactive compounds on stimulator of interferon genes (STING) activation may not depend on ALK. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aar4321

    authors: Blasco RB,Patrucco E,Mota I,Tai WT,Chiarle R

    更新日期:2018-12-12 00:00:00

  • Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice.

    abstract::Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, wher...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aav1866

    authors: Lionello VM,Nicot AS,Sartori M,Kretz C,Kessler P,Buono S,Djerroud S,Messaddeq N,Koebel P,Prokic I,Hérault Y,Romero NB,Laporte J,Cowling BS

    更新日期:2019-03-20 00:00:00

  • Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice.

    abstract::Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as al...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aas9164

    authors: Reyes NJ,Yu C,Mathew R,Kunnen CM,Kalnitsky J,Redfern RL,Leonardi A,Perez VL,MacLeod AS,Gupta PK,Saban DR

    更新日期:2018-07-25 00:00:00

  • Immune-mediated pathology in Duchenne muscular dystrophy.

    abstract::Immunological and inflammatory processes downstream of dystrophin deficiency as well as metabolic abnormalities, defective autophagy, and loss of regenerative capacity all contribute to muscle pathology in Duchenne muscular dystrophy (DMD). These downstream cascades offer potential avenues for pharmacological interven...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aaa7322

    authors: Rosenberg AS,Puig M,Nagaraju K,Hoffman EP,Villalta SA,Rao VA,Wakefield LM,Woodcock J

    更新日期:2015-08-05 00:00:00

  • Off-target lapatinib activity sensitizes colon cancer cells through TRAIL death receptor up-regulation.

    abstract::Lapatinib, a dual HER2/EGFR (human epidermal growth factor receptor 2/epidermal growth factor receptor) inhibitor, is a recently approved targeted therapy for metastatic breast cancer. Because lapatinib enhances the efficacy of the chemotherapeutic agent capecitabine in breast cancer patients, we tested whether lapati...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3001384

    authors: Dolloff NG,Mayes PA,Hart LS,Dicker DT,Humphreys R,El-Deiry WS

    更新日期:2011-06-08 00:00:00

  • More than baby steps: perspectives on pediatric translational research.

    abstract::Although children represent 25% of the U.S. population and nearly 40% of the world's population, pediatric product development typically lags behind that targeted at adults. Here the authors describe the challenges and opportunities of pediatric product development and the unique issues that surround pediatric researc...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000152

    authors: Connor E,Lombardi D,van den Anker J

    更新日期:2009-10-14 00:00:00

  • STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade.

    abstract::Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce r...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa4306

    authors: Fu J,Kanne DB,Leong M,Glickman LH,McWhirter SM,Lemmens E,Mechette K,Leong JJ,Lauer P,Liu W,Sivick KE,Zeng Q,Soares KC,Zheng L,Portnoy DA,Woodward JJ,Pardoll DM,Dubensky TW Jr,Kim Y

    更新日期:2015-04-15 00:00:00

  • Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer's disease trigger BACE1 accumulation in axonal swellings.

    abstract::Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 g...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aba1871

    authors: Lomoio S,Willen R,Kim W,Ho KZ,Robinson EK,Prokopenko D,Kennedy ME,Tanzi RE,Tesco G

    更新日期:2020-11-18 00:00:00