Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs.

Abstract:

:Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy of new antiviral drugs and vaccines. ALX-0171 is a trivalent Nanobody targeting the hRSV fusion (F) protein and its therapeutic potential was evaluated in newborn lambs infected with a human strain of RSV followed by daily ALX-0171 nebulization for 3 or 5 consecutive days. Colostrum-deprived newborn lambs were infected with hRSV-M37 before being treated by daily nebulization with either ALX-0171 or placebo. Two different treatment regimens were examined: day 1-5 or day 3-5 post-infection. Lambs were monitored daily for general well-being and clinical parameters. Respiratory tissues and bronchoalveolar lavage fluid were collected at day 6 post-inoculation for the quantification of viral lesions, lung viral titers, viral antigen and lung histopathology. Administration by inhalation of ALX-0171 was well-tolerated in these hRSV-infected newborn lambs. Robust antiviral effects and positive effects on hRSV-induced lung lesions and reduction in symptoms of illness were noted. These effects were still apparent when treatment start was delayed and coincided with peak viral loads (day 3 post-infection) and at a time point when signs of RSV disease were apparent. The latter design is expected to have high translational value for planned clinical trials. These results are indicative of the therapeutic potential of ALX-0171 in infants.

journal_name

MAbs

journal_title

mAbs

authors

Larios Mora A,Detalle L,Gallup JM,Van Geelen A,Stohr T,Duprez L,Ackermann MR

doi

10.1080/19420862.2018.1470727

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

778-795

issue

5

eissn

1942-0862

issn

1942-0870

journal_volume

10

pub_type

杂志文章

相关文献

mAbs文献大全
  • Preclinical pharmacokinetics, pharmacodynamics, tissue distribution, and tumor penetration of anti-PD-L1 monoclonal antibody, an immune checkpoint inhibitor.

    abstract::MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with programmed cell death-1 (PD-1) and B7.1. It is being investigated as a potential therapy for locally advanced or metastatic malignancies. The purpose ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2015.1136043

    authors: Deng R,Bumbaca D,Pastuskovas CV,Boswell CA,West D,Cowan KJ,Chiu H,McBride J,Johnson C,Xin Y,Koeppen H,Leabman M,Iyer S

    更新日期:2016-01-01 00:00:00

  • American Association of Pharmaceutical Scientists National Biotechnology Conference Short Course: Translational Challenges in Developing Antibody-Drug Conjugates: May 24, 2012, San Diego, CA.

    abstract::The American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference Short Course "Translational Challenges in Developing Antibody-Drug Conjugates (ADCs)," held May 24, 2012 in San Diego, CA, was organized by members of the Pharmacokinetics, Pharmacodynamics and Drug Metabolism section of AAP...

    journal_title:mAbs

    pub_type:

    doi:10.4161/mabs.22909

    authors: Thudium K,Bilic S,Leipold D,Mallet W,Kaur S,Meibohm B,Erickson H,Tibbitts J,Zhao H,Gupta M

    更新日期:2013-01-01 00:00:00

  • Comparing CDRH3 diversity captured from secondary lymphoid organs for the generation of recombinant human antibodies.

    abstract::The plasticity of natural immunoglobulin repertoires can be exploited for the generation of phage display libraries. Secondary lymphoid organs, such as the spleen and the lymph nodes, constitute interesting sources of diversity because they are rich in B cells, part of which can be affinity matured. These organs, howe...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.25592

    authors: Venet S,Kosco-Vilbois M,Fischer N

    更新日期:2013-09-01 00:00:00

  • IgE immunotherapy: a novel concept with promise for the treatment of cancer.

    abstract::The importance of antibodies in activating immune responses against tumors is now better appreciated with the emergence of checkpoint blockade antibodies and with engineered antibody Fc domains featuring enhanced capacity to focus potent effector cells against cancer cells. Antibodies designed with Fc regions of the I...

    journal_title:mAbs

    pub_type: 杂志文章,评审

    doi:10.4161/mabs.27029

    authors: Josephs DH,Spicer JF,Karagiannis P,Gould HJ,Karagiannis SN

    更新日期:2014-01-01 00:00:00

  • Investigation of the effect of salt additives in Protein L affinity chromatography for the purification of tandem single-chain variable fragment bispecific antibodies.

    abstract::Tandem single-chain variable fragment (scFv) bispecific antibodies (bsAb) are one of the most promising bsAb formats reported thus far. Yet, because of their increased aggregation propensity, high impurity content due to low expression level, smaller size and lack of the Fc region, it is challenging to isolate these p...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2020.1718440

    authors: Chen SW,Tan D,Yang YS,Zhang W

    更新日期:2020-01-01 00:00:00

  • Improved in vitro and in vivo activity against CD303-expressing targets of the chimeric 122A2 antibody selected for specific glycosylation pattern.

    abstract::Plasmacytoid dendritic cells (pDCs) play a central role for both innate and adaptive antiviral responses, as they direct immune responses through their unique ability to produce substantial concentrations of type I interferon (IFNs) upon viral encounter while also activating multiple immune cells, including macrophage...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2018.1451283

    authors: Fournier N,Jacque E,Fontayne A,Derache D,Dupont G,Verhaeghe L,Baptista L,Dehenne A,Dezetter AS,Terrier A,Longue A,Pochet-Beghin V,Beghin C,Chtourou S,de Romeuf C

    更新日期:2018-05-01 00:00:00

  • A novel human monoclonal antibody specific to the A33 glycoprotein recognizes colorectal cancer and inhibits metastasis.

    abstract::Colorectal cancer represents the second most common cause of cancer-related death. The human A33 transmembrane glycoprotein is a validated tumor-associated antigen, expressed in 95% of primary and metastatic colorectal cancers. Using phage display technology, we generated a human monoclonal antibody (termed A2) specif...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2020.1714371

    authors: Murer P,Plüss L,Neri D

    更新日期:2020-01-01 00:00:00

  • Reconstructing and mining the B cell repertoire with ImmunediveRsity.

    abstract::The B cell antigen receptor repertoire is highly diverse and constantly modified by clonal selection. High-throughput DNA sequencing (HTS) of the lymphocyte repertoire (Rep-Seq) represents a promising technology to explore such diversity ex-vivo and assist in the identification of antigen-specific antibodies based on ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2015.1026502

    authors: Cortina-Ceballos B,Godoy-Lozano EE,Sámano-Sánchez H,Aguilar-Salgado A,Velasco-Herrera Mdel C,Vargas-Chávez C,Velázquez-Ramírez D,Romero G,Moreno J,Téllez-Sosa J,Martínez-Barnetche J

    更新日期:2015-01-01 00:00:00

  • Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors.

    abstract::In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resista...

    journal_title:mAbs

    pub_type: 杂志文章,随机对照试验

    doi:10.4161/mabs.3.1.14021

    authors: Wang C,He X,Zhou B,Li J,Li B,Qian W,Hou S,Wang H,Shi Y,Guo Y

    更新日期:2011-01-01 00:00:00

  • Galactosylation variations in marketed therapeutic antibodies.

    abstract::There are currently ~25 recombinant full-length IgGs (rIgGs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. Most of these are based on IgG1k framework and are either chimeric, humanized or human antibodies manufactured using either Chinese hamster ovary...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.19868

    authors: Raju TS,Jordan RE

    更新日期:2012-05-01 00:00:00

  • A human monoclonal antibody against small envelope protein of hepatitis B virus with potent neutralization effect.

    abstract::Hepatitis B virus (HBV) produces large (L), middle (M), and small (S) envelope proteins, alternatively referred to as hepatitis B surface antigen (HBsAg). Currently, yeast-derived S protein serves as the preventive vaccine, while hepatitis B immune globulin (HBIG) concentrated from pooled plasma of vaccine recipients ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2015.1134409

    authors: Wang W,Sun L,Li T,Ma Y,Li J,Liu Y,Li M,Wang L,Li C,Xie Y,Wen Y,Liang M,Chen L,Tong S

    更新日期:2016-01-01 00:00:00

  • Computational tool for the early screening of monoclonal antibodies for their viscosities.

    abstract::Highly concentrated antibody solutions often exhibit high viscosities, which present a number of challenges for antibody-drug development, manufacturing and administration. The antibody sequence is a key determinant for high viscosity of highly concentrated solutions; therefore, a sequence- or structure-based tool tha...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2015.1099773

    authors: Agrawal NJ,Helk B,Kumar S,Mody N,Sathish HA,Samra HS,Buck PM,Li L,Trout BL

    更新日期:2016-01-01 00:00:00

  • Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest.

    abstract::While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to th...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.28257

    authors: Derfus GE,Dizon-Maspat J,Broddrick JT,Velayo AC,Toschi JD,Santuray RT,Hsu SK,Winter CM,Krishnan R,Amanullah A

    更新日期:2014-05-01 00:00:00

  • An efficient method for variable region assembly in the construction of scFv phage display libraries using independent strand amplification.

    abstract::Phage display library technology is a common method to produce human antibodies. In this technique, the immunoglobulin variable regions are displayed in a bacteriophage in a way that each filamentous virus displays the product of a single antibody gene on its surface. From the collection of different phages, it is pos...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.20653

    authors: Sotelo P,Collazo N,Zuñiga R,Gutiérrez-González M,Catalán D,Ribeiro CH,Aguillón JC,Molina MC

    更新日期:2012-07-01 00:00:00

  • Expression of antibodies using single open reading frame (sORF) vector design: Demonstration of manufacturing feasibility.

    abstract::Efficient production of large quantities of therapeutic antibodies is becoming a major goal of the pharmaceutical industry. We developed a proprietary expression system using a polyprotein precursor-based approach to antibody expression in mammalian cells. In this approach, the coding regions for heavy and light chain...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.25161

    authors: Gion WR,Davis-Taber RA,Regier DA,Fung E,Medina L,Santora LC,Bose S,Ivanov AV,Perilli-Palmer BA,Chumsae CM,Matuck JG,Kunes YZ,Carson GR

    更新日期:2013-07-01 00:00:00

  • Antibody adsorption on the surface of water studied by neutron reflection.

    abstract::Surface and interfacial adsorption of antibody molecules could cause structural unfolding and desorbed molecules could trigger solution aggregation, resulting in the compromise of physical stability. Although antibody adsorption is important and its relevance to many mechanistic processes has been proposed, few techni...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1276141

    authors: Smith C,Li Z,Holman R,Pan F,Campbell RA,Campana M,Li P,Webster JR,Bishop S,Narwal R,Uddin S,van der Walle CF,Lu JR

    更新日期:2017-04-01 00:00:00

  • Target-independent variable region mediated effects on antibody clearance can be FcRn independent.

    abstract::The importance of the neonatal Fc receptor (FcRn) in extending the serum half-life of monoclonal antibodies (mAbs) is well demonstrated, and has led to the development of multiple engineering approaches designed to alter Fc interactions with FcRn. Recent reports have additionally highlighted the effect of nonspecific ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1208330

    authors: Kelly RL,Yu Y,Sun T,Caffry I,Lynaugh H,Brown M,Jain T,Xu Y,Wittrup KD

    更新日期:2016-10-01 00:00:00

  • Evaluating imbalances of adverse events during biosimilar development.

    abstract::Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1171431

    authors: Vana AM,Freyman AW,Reich SD,Yin D,Li R,Anderson S,Jacobs IA,Zacharchuk CM,Ewesuedo R

    更新日期:2016-07-01 00:00:00

  • Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan.

    abstract::Antibody-drug conjugates (ADCs) that exploit the active metabolite SN-38, which is derived from the popular anticancer drug, irinotecan (a camptothecin that inhibits the nuclear topoisomerase I enzyme, inducing double-stranded DNA breaks during the mitotic S-phase of affected cells), represent a substantial advance in...

    journal_title:mAbs

    pub_type: 杂志文章,评审

    doi:10.1080/19420862.2019.1632115

    authors: Goldenberg DM,Sharkey RM

    更新日期:2019-08-01 00:00:00

  • Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits tumor progression and angiogenesis.

    abstract::Several angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway have been approved for cancer treatment. However, VEGF inhibitors alone were shown to promote tumor invasion and metastasis by increasing intratumoral hypoxia in some preclinical and clinical studies. Emerging rep...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1171432

    authors: Lee D,Kim D,Choi YB,Kang K,Sung ES,Ahn JH,Goo J,Yeom DH,Jang HS,Moon KD,Lee SH,You WK

    更新日期:2016-07-01 00:00:00

  • Design and characterization of mouse IgG1 and IgG2a bispecific antibodies for use in syngeneic models.

    abstract::The development of antibody therapeutics relies on animal models that accurately recapitulate disease biology. Syngeneic mouse models are increasingly used with new molecules to capture the biology of complex cancers and disease states, and to provide insight into the role of the immune system. The establishment of sy...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2019.1685350

    authors: Wang F,Tsai JC,Davis JH,Chau B,Dong J,West SM,Hogan JM,Wheeler ML,Bee C,Morishige W,Cayton T,David-Brown D,Zhang C,Kozhich A,Sproul T,Dollinger G,Rajpal A,Strop P

    更新日期:2020-01-01 00:00:00

  • Specific and high-resolution identification of monoclonal antibody fragments detected by capillary electrophoresis-sodium dodecyl sulfate using reversed-phase HPLC with top-down mass spectrometry analysis.

    abstract::In recent years, capillary electrophoresis-sodium dodecyl sulfate (cSDS) has been widely used for high resolution separation and quantification of the fragments and aggregates of monoclonal antibodies (mAbs) to ensure the quality of mAb therapeutics. However, identification of the low-molecular-weight (LMW) and high-m...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2019.1646554

    authors: Wang WH,Cheung-Lau J,Chen Y,Lewis M,Tang QM

    更新日期:2019-10-01 00:00:00

  • Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies.

    abstract::Although there are currently more than 30 antibody-drug conjugates (ADC) in clinical development for the treatment of blood cancers and solid tumors, comparison of their clinical pharmacokinetics (PK) is challenging because of the large number of, and differences between, the targets, ADC constructs, dosing regimens, ...

    journal_title:mAbs

    pub_type: 杂志文章,评审

    doi:10.4161/mabs.28965

    authors: Deslandes A

    更新日期:2014-07-01 00:00:00

  • A two-in-one antibody engineered from a humanized interleukin 4 antibody through mutation in heavy chain complementarity-determining regions.

    abstract::A mono-specific antibody may recruit a second antigen binding specificity, thus converting to a dual-specific Two-in-One antibody through mutation at the light chain complementarity-determining regions (CDRs). It is, however, unknown whether mutation at the heavy chain CDRs may evolve such dual specificity. Herein, we...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.28483

    authors: Lee CV,Koenig P,Fuh G

    更新日期:2014-05-01 00:00:00

  • Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies.

    abstract::Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs)...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1193660

    authors: Avery LB,Wang M,Kavosi MS,Joyce A,Kurz JC,Fan YY,Dowty ME,Zhang M,Zhang Y,Cheng A,Hua F,Jones HM,Neubert H,Polzer RJ,O'Hara DM

    更新日期:2016-08-01 00:00:00

  • Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology.

    abstract::Neutralizing antibody responses to the surface glycoproteins of enveloped viruses play an important role in immunity. Many of these glycoproteins, including the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) protein form trimeric units in the membrane of the native virion. There is substantial expe...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.2.1.10788

    authors: Berry JD,Hay K,Rini JM,Yu M,Wang L,Plummer FA,Corbett CR,Andonov A

    更新日期:2010-01-01 00:00:00

  • Differences in N-glycan structures found on recombinant IgA1 and IgA2 produced in murine myeloma and CHO cell lines.

    abstract::The development and production of recombinant monoclonal antibodies is well established. Although most of these are IgGs, there is also great interest in producing recombinant IgAs since this isotype plays a critical role in providing immunologic protection at mucosal surfaces. The choice of expression system for prod...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.2.3.11802

    authors: Yoo EM,Yu LJ,Wims LA,Goldberg D,Morrison SL

    更新日期:2010-05-01 00:00:00

  • CD40- and CD95-specific antibody single chain-Baff fusion proteins display BaffR-, TACI- and BCMA-restricted agonism.

    abstract::Antibodies that target a clinically relevant group of receptors within the tumor necrosis factor receptor superfamily (TNFRSF), including CD40 and CD95 (Fas/Apo-1), also require binding to Fc gamma receptors (FcγRs) to elicit a strong agonistic activity. This FcγR dependency largely relies on the mere cellular anchori...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2020.1807721

    authors: Nelke J,Medler J,Weisenberger D,Beilhack A,Wajant H

    更新日期:2020-01-01 00:00:00

  • Analytical FcRn affinity chromatography for functional characterization of monoclonal antibodies.

    abstract::The neonatal Fc receptor (FcRn) is important for the metabolic fate of IgG antibodies in vivo. Analysis of the interaction between FcRn and IgG in vitro might provide insight into the structural and functional integrity of therapeutic IgG that may affect pharmacokinetics (PK) in vivo. We developed a standardized pH gr...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.24981

    authors: Schlothauer T,Rueger P,Stracke JO,Hertenberger H,Fingas F,Kling L,Emrich T,Drabner G,Seeber S,Auer J,Koch S,Papadimitriou A

    更新日期:2013-07-01 00:00:00

  • A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma.

    abstract::The critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients in whom IgE neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total IgE levels or body mass. In this study, we sought...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.28394

    authors: Cohen ES,Dobson CL,Käck H,Wang B,Sims DA,Lloyd CO,England E,Rees DG,Guo H,Karagiannis SN,O'Brien S,Persdotter S,Ekdahl H,Butler R,Keyes F,Oakley S,Carlsson M,Briend E,Wilkinson T,Anderson IK,Monk PD,von Wachenfe

    更新日期:2014-05-01 00:00:00