For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
23
views
36
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      336
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Genetically delivered antibody protects against West Nile virus

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Gene-based delivery of recombinant antibody genes is a promising therapeutic strategy offering numerous advantages including sustained antibody levels, better safety profile and lower production cost. Here we describe generation of a recombinant antibody Fc-9E2 comprising a fusion protein between human Fc of IgG1 and a single-chain Fv derived from a hybridoma 9E2 secreting a mAb neutralizing West Nile virus (WNV). Fc-9E2 was shown to retain parental mAb's specificity and WNV-neutralizing capacity. Adenovirus-mediated in vivo delivery of the antibody gene resulted in sustained Fc-9E2 serum levels leading to abrogation of lethal WNV infection in an animal model.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus

          Theodore Oliphant, Michael Engle, Grant Nybakken … (2005)
          Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated monoclonal antibodies against domain III of the WNV E protein. Monoclonal antibodies that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from individuals who had recovered from WNV infection also detected this epitope. One monoclonal antibody, E16, neutralized 10 different strains in vitro, and showed therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity and neutralizing activity. In postexposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and may therefore be a viable treatment option against WNV infection in humans. Supplementary information The online version of this article (doi:10.1038/nm1240) contains supplementary material, which is available to authorized users.
          Article 0 comments Cited 157 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells.

            W. Crill, J. Roehrig (2001)
            The specific mechanisms by which antibodies neutralize flavivirus infectivity are not completely understood. To study these mechanisms in more detail, we analyzed the ability of a well-defined set of anti-dengue (DEN) virus E-glycoprotein-specific monoclonal antibodies (MAbs) to block virus adsorption to Vero cells. In contrast to previous studies, the binding sites of these MAbs were localized to one of three structural domains (I, II, and III) in the E glycoprotein. The results indicate that most MAbs that neutralize virus infectivity do so, at least in part, by the blocking of virus adsorption. However, MAbs specific for domain III were the strongest blockers of virus adsorption. These results extend our understanding of the structure-function relationships in the E glycoprotein of DEN virus and provide the first direct evidence that domain III encodes the primary flavivirus receptor-binding motif.
            Article 0 comments Cited 154 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract.

              Robert M. Woods, Syd Johnson, Emma Young … (2007)
              Respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis and pneumonia in infants and children. Currently, palivizumab is the only approved monoclonal antibody (mAb) for prophylaxis of RSV. However, a small percentage of patients are not protected by palivizumab; in addition, palivizumab does not inhibit RSV replication effectively in the upper respiratory tract. We report here the development and characterization of motavizumab, an ultra-potent, affinity-matured, humanized mAb derived from palivizumab. Several palivizumab variants that enhanced the neutralization of RSV in vitro by up to 44-fold were generated; however, in vivo prophylaxis of cotton rats with these antibodies conferred only about a twofold improvement in potency over palivizumab. This unexpected small increase of in vivo potency was caused by poor serum pharmacokinetics and lung bio-availability that resulted from unexpectedly broad tissue binding. Subsequent analyses revealed that changes at three amino acids arising from the affinity maturation markedly increased the non-specific binding to various tissues. Our results suggested that k(on)-driven mutations are more likely to initiate non-specific binding events than k(off)-driven mutations. Reversion of these three residues to the original sequences greatly diminished the tissue binding. The resulting mAb, motavizumab, binds to RSV F protein 70-fold better than palivizumab, and exhibits about a 20-fold improvement in neutralization of RSV in vitro. In cotton rats, at equivalent concentrations, motavizumab reduced pulmonary RSV titers to up to 100-fold lower levels than did palivizumab and, unlike palivizumab, motavizumab very potently inhibited viral replication in the upper respiratory tract. This affinity-enhanced mAb is being investigated in pivotal clinical trials. Importantly, our engineering process offers precious insights into the improvement of other therapeutic mAbs.
              Article 0 comments Cited 134 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Alexander Pereboev
                Journal
                Journal ID (nlm-ta): Antiviral Res
                Journal ID (iso-abbrev): Antiviral Res
                Title: Antiviral Research
                Publisher: Elsevier B.V.
                ISSN (Print): 0166-3542
                ISSN (Electronic): 1872-9096
                Publication date PMC-release: 14 September 2007
                Publication date (Print): January 2008
                Publication date (Electronic): 14 September 2007
                Volume: 77
                Issue: 1
                Pages: 6-13
                Affiliations
                [a ]Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA
                [b ]Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA
                [c ]State Research Center of Virology and Biotechnology “Vector”, Koltsovo, Novosibirsk, Russia
                Author notes
                [* ]Corresponding author at: University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35294-2172, USA. Tel.: +1 205 975 8734; fax: +1 205 975 8565. pereboev@ 123456uab.edu
                Article
                Publisher ID: S0166-3542(07)00402-0
                DOI: 10.1016/j.antiviral.2007.08.010
                PMC ID: 2267767
                PubMed ID: 17904654
                SO-VID: 5ee2b692-8533-4e15-adde-65e8bf0b5dc2
                Copyright © Copyright © 2007 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 15 July 2007
                Date accepted : 22 August 2007
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: wnv, west nile virus,ad, adenovirus,recab, recombinant antibody,scfv, single chain fragment variable,fc, fragment crystallizable,wnvec, c-terminal fragment of wnv e protein,prnt, plaque reduction-neutralization test,wnv,passive immunization,recombinant antibody,gene delivery,adenovirus
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: wnv, west nile virus, ad, adenovirus, recab, recombinant antibody, scfv, single chain fragment variable, fc, fragment crystallizable, wnvec, c-terminal fragment of wnv e protein, prnt, plaque reduction-neutralization test, wnv, passive immunization, recombinant antibody, gene delivery, adenovirus

                Comments

                Comment on this article

                scite_

                Similar content336

                See all similar

                Cited by3

                See all cited by

                Most referenced authors716

                See all reference authors