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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1997-2-4
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pubmed:databankReference | |
pubmed:abstractText |
Several antibody-dependent mechanisms have been postulated to mediate neutralization of different animal viruses, including blocking of docking to receptors, induction of conformational changes in the virus coat, and Fc-dependent opsonization. We have studied the molecular requirements for antibody-mediated neutralization of vesicular stomatitis virus (VSV) in vitro and protection against lethal disease in vivo with a single-chain Fv fragment (scFv) and the corresponding bivalent miniantibody (scFv-dHLX) generated from a VSV-neutralizing monoclonal antibody. Both monovalent scFv and bivalent scFv-dHLX miniantibodies were able to neutralize VSV in vitro and to protect interferon-alphabeta receptor-deficient (IFN-alphabeta R-/-) mice against lethal disease after intravenous injection of 50 plaque-forming units (pfu) VSV pre-incubated with the scFv reagents. Similarly, severe-combined immunodeficient (SCID) mice infected with immune complexes of 10(8) pfu VSV and bivalent scFv-dHLX were protected against lethal disease; however, mice infected with immune complexes of 10(8) pfu VSV and monovalent scFv were not. Although repeated scFv-dHLX treatment reduced virus quantities in the blood, neither SCID nor IFN-alphabeta R-/- mice were protected against lethal disease after passive immunization and subsequent VSV infection. This was due to the short half-life of 17 min of scFv-dHLX in the circulation. These data demonstrate that neutralization of VSV and protection against lethal disease do not require Fc-mediated mechanisms and that cross-linking is not crucial for protection against physiologically relevant virus doses in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0014-2980
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2801-6
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8977271-Amino Acid Sequence,
pubmed-meshheading:8977271-Animals,
pubmed-meshheading:8977271-Antibodies, Monoclonal,
pubmed-meshheading:8977271-Antibodies, Viral,
pubmed-meshheading:8977271-Binding, Competitive,
pubmed-meshheading:8977271-Immunoglobulin Fragments,
pubmed-meshheading:8977271-Immunoglobulin Variable Region,
pubmed-meshheading:8977271-Mice,
pubmed-meshheading:8977271-Mice, Inbred BALB C,
pubmed-meshheading:8977271-Mice, SCID,
pubmed-meshheading:8977271-Molecular Sequence Data,
pubmed-meshheading:8977271-Rhabdoviridae Infections,
pubmed-meshheading:8977271-Vesicular stomatitis Indiana virus
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pubmed:year |
1996
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pubmed:articleTitle |
Monovalent single-chain Fv fragments and bivalent miniantibodies bound to vesicular stomatitis virus protect against lethal infection.
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pubmed:affiliation |
Institute of Experimental Immunology, Department of Pathology, University of Zürich, Switzerland. ukalinke@usz.unizh.ch
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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