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Efficient In Vitro and In Vivo Activity of Glyco-Engineered Plant-Produced Rabies Monoclonal Antibodies E559 and 62-71-3.

Identifieur interne : 000300 ( Main/Exploration ); précédent : 000299; suivant : 000301

Efficient In Vitro and In Vivo Activity of Glyco-Engineered Plant-Produced Rabies Monoclonal Antibodies E559 and 62-71-3.

Auteurs : Tsepo Lebiletsa Tsekoa [Afrique du Sud] ; Therese Lotter-Stark [Afrique du Sud] ; Sindisiwe Buthelezi [Afrique du Sud] ; Ereck Chakauya [Afrique du Sud] ; Stoyan H. Stoychev [Afrique du Sud] ; Claude Sabeta [Afrique du Sud] ; Wonderful Shumba [Afrique du Sud] ; Baby Phahladira [Afrique du Sud] ; Steve Hume [États-Unis] ; Josh Morton [États-Unis] ; Charles E. Rupprecht [États-Unis] ; Herta Steinkellner [Autriche] ; Michael Pauly [États-Unis] ; Larry Zeitlin [États-Unis] ; Kevin Whaley [États-Unis] ; Rachel Chikwamba [Afrique du Sud]

Source :

RBID : pubmed:27427976

Descripteurs français

English descriptors

Abstract

Rabies is a neglected zoonotic disease that has no effective treatment after onset of illness. However the disease can be prevented effectively by prompt administration of post exposure prophylaxis which includes administration of passive immunizing antibodies (Rabies Immune Globulin, RIG). Currently, human RIG suffers from many restrictions including limited availability, batch-to batch inconsistencies and potential for contamination with blood-borne pathogens. Anti-rabies monoclonal antibodies (mAbs) have been identified as a promising alternative to RIG. Here, we applied a plant-based transient expression system to achieve rapid, high level production and efficacy of the two highly potent anti-rabies mAbs E559 and 62-71-3. Expression levels of up to 490 mg/kg of recombinant mAbs were obtained in Nicotiana benthamiana glycosylation mutants by using a viral based transient expression system. The plant-made E559 and 62-71-3, carrying human-type fucose-free N-glycans, assembled properly and were structurally sound as determined by mass spectrometry and calorimetric density measurements. Both mAbs efficiently neutralised diverse rabies virus variants in vitro. Importantly, E559 and 62-71-3 exhibited enhanced protection against rabies virus compared to human RIG in a hamster model post-exposure challenge trial. Collectively, our results provide the basis for the development of a multi-mAb based alternative to RIG.

DOI: 10.1371/journal.pone.0159313
PubMed: 27427976
PubMed Central: PMC4948892


Affiliations:


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Le document en format XML

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<name sortKey="Sabeta, Claude" sort="Sabeta, Claude" uniqKey="Sabeta C" first="Claude" last="Sabeta">Claude Sabeta</name>
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<name sortKey="Shumba, Wonderful" sort="Shumba, Wonderful" uniqKey="Shumba W" first="Wonderful" last="Shumba">Wonderful Shumba</name>
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<name sortKey="Phahladira, Baby" sort="Phahladira, Baby" uniqKey="Phahladira B" first="Baby" last="Phahladira">Baby Phahladira</name>
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<name sortKey="Hume, Steve" sort="Hume, Steve" uniqKey="Hume S" first="Steve" last="Hume">Steve Hume</name>
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<nlm:affiliation>Kentucky Bioprocessing, Owensboro, Kentucky, United States.</nlm:affiliation>
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<name sortKey="Morton, Josh" sort="Morton, Josh" uniqKey="Morton J" first="Josh" last="Morton">Josh Morton</name>
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<nlm:affiliation>Kentucky Bioprocessing, Owensboro, Kentucky, United States.</nlm:affiliation>
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<name sortKey="Rupprecht, Charles E" sort="Rupprecht, Charles E" uniqKey="Rupprecht C" first="Charles E" last="Rupprecht">Charles E. Rupprecht</name>
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<nlm:affiliation>The Wistar Institute, Philadelphia, Pennsylvania, United States.</nlm:affiliation>
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<name sortKey="Steinkellner, Herta" sort="Steinkellner, Herta" uniqKey="Steinkellner H" first="Herta" last="Steinkellner">Herta Steinkellner</name>
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<nlm:affiliation>Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
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<name sortKey="Zeitlin, Larry" sort="Zeitlin, Larry" uniqKey="Zeitlin L" first="Larry" last="Zeitlin">Larry Zeitlin</name>
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<nlm:affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</nlm:affiliation>
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<region type="state">Californie</region>
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<name sortKey="Whaley, Kevin" sort="Whaley, Kevin" uniqKey="Whaley K" first="Kevin" last="Whaley">Kevin Whaley</name>
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<nlm:affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</nlm:affiliation>
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<name sortKey="Chikwamba, Rachel" sort="Chikwamba, Rachel" uniqKey="Chikwamba R" first="Rachel" last="Chikwamba">Rachel Chikwamba</name>
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<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
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<title xml:lang="en">Efficient In Vitro and In Vivo Activity of Glyco-Engineered Plant-Produced Rabies Monoclonal Antibodies E559 and 62-71-3.</title>
<author>
<name sortKey="Tsekoa, Tsepo Lebiletsa" sort="Tsekoa, Tsepo Lebiletsa" uniqKey="Tsekoa T" first="Tsepo Lebiletsa" last="Tsekoa">Tsepo Lebiletsa Tsekoa</name>
<affiliation wicri:level="1">
<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
<wicri:noRegion>Pretoria</wicri:noRegion>
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<name sortKey="Lotter Stark, Therese" sort="Lotter Stark, Therese" uniqKey="Lotter Stark T" first="Therese" last="Lotter-Stark">Therese Lotter-Stark</name>
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<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
<wicri:noRegion>Pretoria</wicri:noRegion>
</affiliation>
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<name sortKey="Buthelezi, Sindisiwe" sort="Buthelezi, Sindisiwe" uniqKey="Buthelezi S" first="Sindisiwe" last="Buthelezi">Sindisiwe Buthelezi</name>
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<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
<wicri:noRegion>Pretoria</wicri:noRegion>
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<name sortKey="Chakauya, Ereck" sort="Chakauya, Ereck" uniqKey="Chakauya E" first="Ereck" last="Chakauya">Ereck Chakauya</name>
<affiliation wicri:level="1">
<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
<wicri:noRegion>Pretoria</wicri:noRegion>
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<name sortKey="Stoychev, Stoyan H" sort="Stoychev, Stoyan H" uniqKey="Stoychev S" first="Stoyan H" last="Stoychev">Stoyan H. Stoychev</name>
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<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
<wicri:noRegion>Pretoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sabeta, Claude" sort="Sabeta, Claude" uniqKey="Sabeta C" first="Claude" last="Sabeta">Claude Sabeta</name>
<affiliation wicri:level="1">
<nlm:affiliation>ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>ARC-Onderstepoort Veterinary Institute, Onderstepoort</wicri:regionArea>
<wicri:noRegion>Onderstepoort</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Shumba, Wonderful" sort="Shumba, Wonderful" uniqKey="Shumba W" first="Wonderful" last="Shumba">Wonderful Shumba</name>
<affiliation wicri:level="1">
<nlm:affiliation>ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>ARC-Onderstepoort Veterinary Institute, Onderstepoort</wicri:regionArea>
<wicri:noRegion>Onderstepoort</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Phahladira, Baby" sort="Phahladira, Baby" uniqKey="Phahladira B" first="Baby" last="Phahladira">Baby Phahladira</name>
<affiliation wicri:level="1">
<nlm:affiliation>ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>ARC-Onderstepoort Veterinary Institute, Onderstepoort</wicri:regionArea>
<wicri:noRegion>Onderstepoort</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hume, Steve" sort="Hume, Steve" uniqKey="Hume S" first="Steve" last="Hume">Steve Hume</name>
<affiliation wicri:level="2">
<nlm:affiliation>Kentucky Bioprocessing, Owensboro, Kentucky, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Kentucky Bioprocessing, Owensboro, Kentucky</wicri:regionArea>
<placeName>
<region type="state">Kentucky</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Morton, Josh" sort="Morton, Josh" uniqKey="Morton J" first="Josh" last="Morton">Josh Morton</name>
<affiliation wicri:level="2">
<nlm:affiliation>Kentucky Bioprocessing, Owensboro, Kentucky, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Kentucky Bioprocessing, Owensboro, Kentucky</wicri:regionArea>
<placeName>
<region type="state">Kentucky</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Rupprecht, Charles E" sort="Rupprecht, Charles E" uniqKey="Rupprecht C" first="Charles E" last="Rupprecht">Charles E. Rupprecht</name>
<affiliation wicri:level="2">
<nlm:affiliation>The Wistar Institute, Philadelphia, Pennsylvania, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Wistar Institute, Philadelphia, Pennsylvania</wicri:regionArea>
<placeName>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Steinkellner, Herta" sort="Steinkellner, Herta" uniqKey="Steinkellner H" first="Herta" last="Steinkellner">Herta Steinkellner</name>
<affiliation wicri:level="3">
<nlm:affiliation>Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna</wicri:regionArea>
<placeName>
<settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pauly, Michael" sort="Pauly, Michael" uniqKey="Pauly M" first="Michael" last="Pauly">Michael Pauly</name>
<affiliation wicri:level="2">
<nlm:affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mapp Biopharmaceutical, San Diego, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zeitlin, Larry" sort="Zeitlin, Larry" uniqKey="Zeitlin L" first="Larry" last="Zeitlin">Larry Zeitlin</name>
<affiliation wicri:level="2">
<nlm:affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mapp Biopharmaceutical, San Diego, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Whaley, Kevin" sort="Whaley, Kevin" uniqKey="Whaley K" first="Kevin" last="Whaley">Kevin Whaley</name>
<affiliation wicri:level="2">
<nlm:affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mapp Biopharmaceutical, San Diego, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Chikwamba, Rachel" sort="Chikwamba, Rachel" uniqKey="Chikwamba R" first="Rachel" last="Chikwamba">Rachel Chikwamba</name>
<affiliation wicri:level="1">
<nlm:affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria</wicri:regionArea>
<wicri:noRegion>Pretoria</wicri:noRegion>
</affiliation>
</author>
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<series>
<title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2016" type="published">2016</date>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Agrobacterium tumefaciens (genetics)</term>
<term>Agrobacterium tumefaciens (metabolism)</term>
<term>Animals (MeSH)</term>
<term>Antibodies, Monoclonal (administration & dosage)</term>
<term>Antibodies, Monoclonal (biosynthesis)</term>
<term>Antibodies, Monoclonal (genetics)</term>
<term>Antibodies, Viral (administration & dosage)</term>
<term>Antibodies, Viral (biosynthesis)</term>
<term>Antibodies, Viral (genetics)</term>
<term>Cloning, Molecular (MeSH)</term>
<term>Female (MeSH)</term>
<term>Gene Expression (MeSH)</term>
<term>Genetic Vectors (chemistry)</term>
<term>Genetic Vectors (metabolism)</term>
<term>Immunization, Passive (MeSH)</term>
<term>Mesocricetus (MeSH)</term>
<term>Neutralization Tests (MeSH)</term>
<term>Plants, Genetically Modified (MeSH)</term>
<term>Rabies (immunology)</term>
<term>Rabies (mortality)</term>
<term>Rabies (prevention & control)</term>
<term>Rabies (virology)</term>
<term>Rabies Vaccines (administration & dosage)</term>
<term>Rabies Vaccines (biosynthesis)</term>
<term>Rabies virus (drug effects)</term>
<term>Rabies virus (growth & development)</term>
<term>Rabies virus (immunology)</term>
<term>Rabies virus (pathogenicity)</term>
<term>Recombinant Proteins (administration & dosage)</term>
<term>Recombinant Proteins (biosynthesis)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Survival Analysis (MeSH)</term>
<term>Tobacco (genetics)</term>
<term>Tobacco (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Agrobacterium tumefaciens (génétique)</term>
<term>Agrobacterium tumefaciens (métabolisme)</term>
<term>Analyse de survie (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Anticorps antiviraux (administration et posologie)</term>
<term>Anticorps antiviraux (biosynthèse)</term>
<term>Anticorps antiviraux (génétique)</term>
<term>Anticorps monoclonaux (administration et posologie)</term>
<term>Anticorps monoclonaux (biosynthèse)</term>
<term>Anticorps monoclonaux (génétique)</term>
<term>Clonage moléculaire (MeSH)</term>
<term>Expression des gènes (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Immunisation passive (MeSH)</term>
<term>Mesocricetus (MeSH)</term>
<term>Protéines recombinantes (administration et posologie)</term>
<term>Protéines recombinantes (biosynthèse)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Rage (maladie) (immunologie)</term>
<term>Rage (maladie) (mortalité)</term>
<term>Rage (maladie) (prévention et contrôle)</term>
<term>Rage (maladie) (virologie)</term>
<term>Tabac (génétique)</term>
<term>Tabac (métabolisme)</term>
<term>Tests de neutralisation (MeSH)</term>
<term>Vaccins antirabiques (administration et posologie)</term>
<term>Vaccins antirabiques (biosynthèse)</term>
<term>Vecteurs génétiques (composition chimique)</term>
<term>Vecteurs génétiques (métabolisme)</term>
<term>Virus de la rage (croissance et développement)</term>
<term>Virus de la rage (effets des médicaments et des substances chimiques)</term>
<term>Virus de la rage (immunologie)</term>
<term>Virus de la rage (pathogénicité)</term>
<term>Végétaux génétiquement modifiés (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Antibodies, Monoclonal</term>
<term>Antibodies, Viral</term>
<term>Rabies Vaccines</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Antibodies, Monoclonal</term>
<term>Antibodies, Viral</term>
<term>Rabies Vaccines</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Protéines recombinantes</term>
<term>Vaccins antirabiques</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Protéines recombinantes</term>
<term>Vaccins antirabiques</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>Genetic Vectors</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr">
<term>Vecteurs génétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr">
<term>Virus de la rage</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Rabies virus</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Virus de la rage</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Agrobacterium tumefaciens</term>
<term>Antibodies, Monoclonal</term>
<term>Antibodies, Viral</term>
<term>Recombinant Proteins</term>
<term>Tobacco</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en">
<term>Rabies virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Agrobacterium tumefaciens</term>
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Protéines recombinantes</term>
<term>Tabac</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Rage (maladie)</term>
<term>Virus de la rage</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Rabies</term>
<term>Rabies virus</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Agrobacterium tumefaciens</term>
<term>Genetic Vectors</term>
<term>Tobacco</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en">
<term>Rabies</term>
</keywords>
<keywords scheme="MESH" qualifier="mortalité" xml:lang="fr">
<term>Rage (maladie)</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Agrobacterium tumefaciens</term>
<term>Tabac</term>
<term>Vecteurs génétiques</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Rabies virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Virus de la rage</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Rabies</term>
</keywords>
<keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr">
<term>Rage (maladie)</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Rage (maladie)</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Rabies</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cloning, Molecular</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Immunization, Passive</term>
<term>Mesocricetus</term>
<term>Neutralization Tests</term>
<term>Plants, Genetically Modified</term>
<term>Survival Analysis</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse de survie</term>
<term>Animaux</term>
<term>Clonage moléculaire</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Immunisation passive</term>
<term>Mesocricetus</term>
<term>Tests de neutralisation</term>
<term>Végétaux génétiquement modifiés</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">Rabies is a neglected zoonotic disease that has no effective treatment after onset of illness. However the disease can be prevented effectively by prompt administration of post exposure prophylaxis which includes administration of passive immunizing antibodies (Rabies Immune Globulin, RIG). Currently, human RIG suffers from many restrictions including limited availability, batch-to batch inconsistencies and potential for contamination with blood-borne pathogens. Anti-rabies monoclonal antibodies (mAbs) have been identified as a promising alternative to RIG. Here, we applied a plant-based transient expression system to achieve rapid, high level production and efficacy of the two highly potent anti-rabies mAbs E559 and 62-71-3. Expression levels of up to 490 mg/kg of recombinant mAbs were obtained in Nicotiana benthamiana glycosylation mutants by using a viral based transient expression system. The plant-made E559 and 62-71-3, carrying human-type fucose-free N-glycans, assembled properly and were structurally sound as determined by mass spectrometry and calorimetric density measurements. Both mAbs efficiently neutralised diverse rabies virus variants in vitro. Importantly, E559 and 62-71-3 exhibited enhanced protection against rabies virus compared to human RIG in a hamster model post-exposure challenge trial. Collectively, our results provide the basis for the development of a multi-mAb based alternative to RIG. </div>
</front>
</TEI>
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<PMID Version="1">27427976</PMID>
<DateCompleted>
<Year>2017</Year>
<Month>07</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised>
<Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection">
<Journal>
<ISSN IssnType="Electronic">1932-6203</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>11</Volume>
<Issue>7</Issue>
<PubDate>
<Year>2016</Year>
</PubDate>
</JournalIssue>
<Title>PloS one</Title>
<ISOAbbreviation>PLoS One</ISOAbbreviation>
</Journal>
<ArticleTitle>Efficient In Vitro and In Vivo Activity of Glyco-Engineered Plant-Produced Rabies Monoclonal Antibodies E559 and 62-71-3.</ArticleTitle>
<Pagination>
<MedlinePgn>e0159313</MedlinePgn>
</Pagination>
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<Abstract>
<AbstractText>Rabies is a neglected zoonotic disease that has no effective treatment after onset of illness. However the disease can be prevented effectively by prompt administration of post exposure prophylaxis which includes administration of passive immunizing antibodies (Rabies Immune Globulin, RIG). Currently, human RIG suffers from many restrictions including limited availability, batch-to batch inconsistencies and potential for contamination with blood-borne pathogens. Anti-rabies monoclonal antibodies (mAbs) have been identified as a promising alternative to RIG. Here, we applied a plant-based transient expression system to achieve rapid, high level production and efficacy of the two highly potent anti-rabies mAbs E559 and 62-71-3. Expression levels of up to 490 mg/kg of recombinant mAbs were obtained in Nicotiana benthamiana glycosylation mutants by using a viral based transient expression system. The plant-made E559 and 62-71-3, carrying human-type fucose-free N-glycans, assembled properly and were structurally sound as determined by mass spectrometry and calorimetric density measurements. Both mAbs efficiently neutralised diverse rabies virus variants in vitro. Importantly, E559 and 62-71-3 exhibited enhanced protection against rabies virus compared to human RIG in a hamster model post-exposure challenge trial. Collectively, our results provide the basis for the development of a multi-mAb based alternative to RIG. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Tsekoa</LastName>
<ForeName>Tsepo Lebiletsa</ForeName>
<Initials>TL</Initials>
<AffiliationInfo>
<Affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lotter-Stark</LastName>
<ForeName>Therese</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Buthelezi</LastName>
<ForeName>Sindisiwe</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Chakauya</LastName>
<ForeName>Ereck</ForeName>
<Initials>E</Initials>
<AffiliationInfo>
<Affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Stoychev</LastName>
<ForeName>Stoyan H</ForeName>
<Initials>SH</Initials>
<AffiliationInfo>
<Affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sabeta</LastName>
<ForeName>Claude</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Shumba</LastName>
<ForeName>Wonderful</ForeName>
<Initials>W</Initials>
<AffiliationInfo>
<Affiliation>ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Phahladira</LastName>
<ForeName>Baby</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>ARC-Onderstepoort Veterinary Institute, Onderstepoort, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hume</LastName>
<ForeName>Steve</ForeName>
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<Affiliation>Kentucky Bioprocessing, Owensboro, Kentucky, United States.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Morton</LastName>
<ForeName>Josh</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Kentucky Bioprocessing, Owensboro, Kentucky, United States.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rupprecht</LastName>
<ForeName>Charles E</ForeName>
<Initials>CE</Initials>
<AffiliationInfo>
<Affiliation>The Wistar Institute, Philadelphia, Pennsylvania, United States.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Steinkellner</LastName>
<ForeName>Herta</ForeName>
<Initials>H</Initials>
<AffiliationInfo>
<Affiliation>Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pauly</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zeitlin</LastName>
<ForeName>Larry</ForeName>
<Initials>L</Initials>
<AffiliationInfo>
<Affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Whaley</LastName>
<ForeName>Kevin</ForeName>
<Initials>K</Initials>
<AffiliationInfo>
<Affiliation>Mapp Biopharmaceutical, San Diego, California, United States.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Chikwamba</LastName>
<ForeName>Rachel</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2016</Year>
<Month>07</Month>
<Day>18</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>PLoS One</MedlineTA>
<NlmUniqueID>101285081</NlmUniqueID>
<ISSNLinking>1932-6203</ISSNLinking>
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<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011819">Rabies Vaccines</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance>
</Chemical>
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<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D016960" MajorTopicYN="N">Agrobacterium tumefaciens</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003001" MajorTopicYN="N">Cloning, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005822" MajorTopicYN="N">Genetic Vectors</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007116" MajorTopicYN="Y">Immunization, Passive</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008647" MajorTopicYN="N">Mesocricetus</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009500" MajorTopicYN="N">Neutralization Tests</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D030821" MajorTopicYN="N">Plants, Genetically Modified</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011818" MajorTopicYN="N">Rabies</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011819" MajorTopicYN="N">Rabies Vaccines</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011820" MajorTopicYN="N">Rabies virus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014026" MajorTopicYN="N">Tobacco</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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<Month>06</Month>
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<li>Californie</li>
<li>Kentucky</li>
<li>Pennsylvanie</li>
<li>Vienne (Autriche)</li>
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<settlement>
<li>Vienne (Autriche)</li>
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<country name="Afrique du Sud">
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<name sortKey="Tsekoa, Tsepo Lebiletsa" sort="Tsekoa, Tsepo Lebiletsa" uniqKey="Tsekoa T" first="Tsepo Lebiletsa" last="Tsekoa">Tsepo Lebiletsa Tsekoa</name>
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<name sortKey="Buthelezi, Sindisiwe" sort="Buthelezi, Sindisiwe" uniqKey="Buthelezi S" first="Sindisiwe" last="Buthelezi">Sindisiwe Buthelezi</name>
<name sortKey="Chakauya, Ereck" sort="Chakauya, Ereck" uniqKey="Chakauya E" first="Ereck" last="Chakauya">Ereck Chakauya</name>
<name sortKey="Chikwamba, Rachel" sort="Chikwamba, Rachel" uniqKey="Chikwamba R" first="Rachel" last="Chikwamba">Rachel Chikwamba</name>
<name sortKey="Lotter Stark, Therese" sort="Lotter Stark, Therese" uniqKey="Lotter Stark T" first="Therese" last="Lotter-Stark">Therese Lotter-Stark</name>
<name sortKey="Phahladira, Baby" sort="Phahladira, Baby" uniqKey="Phahladira B" first="Baby" last="Phahladira">Baby Phahladira</name>
<name sortKey="Sabeta, Claude" sort="Sabeta, Claude" uniqKey="Sabeta C" first="Claude" last="Sabeta">Claude Sabeta</name>
<name sortKey="Shumba, Wonderful" sort="Shumba, Wonderful" uniqKey="Shumba W" first="Wonderful" last="Shumba">Wonderful Shumba</name>
<name sortKey="Stoychev, Stoyan H" sort="Stoychev, Stoyan H" uniqKey="Stoychev S" first="Stoyan H" last="Stoychev">Stoyan H. Stoychev</name>
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<country name="États-Unis">
<region name="Kentucky">
<name sortKey="Hume, Steve" sort="Hume, Steve" uniqKey="Hume S" first="Steve" last="Hume">Steve Hume</name>
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<name sortKey="Morton, Josh" sort="Morton, Josh" uniqKey="Morton J" first="Josh" last="Morton">Josh Morton</name>
<name sortKey="Pauly, Michael" sort="Pauly, Michael" uniqKey="Pauly M" first="Michael" last="Pauly">Michael Pauly</name>
<name sortKey="Rupprecht, Charles E" sort="Rupprecht, Charles E" uniqKey="Rupprecht C" first="Charles E" last="Rupprecht">Charles E. Rupprecht</name>
<name sortKey="Whaley, Kevin" sort="Whaley, Kevin" uniqKey="Whaley K" first="Kevin" last="Whaley">Kevin Whaley</name>
<name sortKey="Zeitlin, Larry" sort="Zeitlin, Larry" uniqKey="Zeitlin L" first="Larry" last="Zeitlin">Larry Zeitlin</name>
</country>
<country name="Autriche">
<region name="Vienne (Autriche)">
<name sortKey="Steinkellner, Herta" sort="Steinkellner, Herta" uniqKey="Steinkellner H" first="Herta" last="Steinkellner">Herta Steinkellner</name>
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