Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody
Identifieur interne : 000559 ( Main/Exploration ); précédent : 000558; suivant : 000560Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody
Auteurs : Sang Il Kim [Corée du Sud] ; Sujeong Kim [Corée du Sud] ; Jinhee Kim ; So Young Chang ; Jung Min Shim ; Jongwha Jin ; Chungsu Lim ; Songyi Baek ; Ji-Young Min ; Wan Beom Park ; Myoung-Don Oh ; Seungtaek Kim ; Junho Chung [Corée du Sud]Source :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Descripteurs français
- KwdFr :
- Administration par inhalation, Animaux, Anticorps antiviraux (administration et posologie), Anticorps antiviraux (génétique), Anticorps antiviraux (immunologie), Anticorps neutralisants (administration et posologie), Anticorps neutralisants (génétique), Anticorps neutralisants (immunologie), Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Humains, Régions déterminant la complémentarité (génétique), Régions déterminant la complémentarité (immunologie).
- MESH :
- administration et posologie : Anticorps antiviraux, Anticorps neutralisants.
- génétique : Anticorps antiviraux, Anticorps neutralisants, Régions déterminant la complémentarité.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Coronavirus du syndrome respiratoire du Moyen-Orient, Régions déterminant la complémentarité.
- Administration par inhalation, Animaux, Cellules Vero, Humains.
English descriptors
- KwdEn :
- Administration, Inhalation, Animals, Antibodies, Neutralizing (administration & dosage), Antibodies, Neutralizing (genetics), Antibodies, Neutralizing (immunology), Antibodies, Viral (administration & dosage), Antibodies, Viral (genetics), Antibodies, Viral (immunology), Chlorocebus aethiops, Complementarity Determining Regions (genetics), Complementarity Determining Regions (immunology), Humans, Middle East Respiratory Syndrome Coronavirus (immunology), Vero Cells.
- MESH :
- chemical , administration & dosage : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Antibodies, Neutralizing, Antibodies, Viral, Complementarity Determining Regions.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Complementarity Determining Regions.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- Administration, Inhalation, Animals, Chlorocebus aethiops, Humans, Vero Cells.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.
Url:
DOI: 10.3390/ijms20205073
PubMed: 31614869
PubMed Central: 6829326
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody</title><author><name sortKey="Kim, Sang Il" sort="Kim, Sang Il" uniqKey="Kim S" first="Sang Il" last="Kim">Sang Il Kim</name><affiliation><nlm:aff id="af1-ijms-20-05073">Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea;<email>sangk1128@snu.ac.kr</email> (S.I.K.);<email>sujeong5425@snu.ac.kr</email> (S.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-05073">Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Sujeong" sort="Kim, Sujeong" uniqKey="Kim S" first="Sujeong" last="Kim">Sujeong Kim</name><affiliation><nlm:aff id="af1-ijms-20-05073">Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea;<email>sangk1128@snu.ac.kr</email> (S.I.K.);<email>sujeong5425@snu.ac.kr</email> (S.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-05073">Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name><affiliation><nlm:aff id="af4-ijms-20-05073">Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jinhee.kim@ip-korea.org</email> (J.K.);<email>soyoung.chang@ip-korea.org</email> (S.Y.C.);<email>ji-young.x.min@gsk.com</email> (J.-Y.M.)</nlm:aff></affiliation></author><author><name sortKey="Chang, So Young" sort="Chang, So Young" uniqKey="Chang S" first="So Young" last="Chang">So Young Chang</name><affiliation><nlm:aff id="af4-ijms-20-05073">Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jinhee.kim@ip-korea.org</email> (J.K.);<email>soyoung.chang@ip-korea.org</email> (S.Y.C.);<email>ji-young.x.min@gsk.com</email> (J.-Y.M.)</nlm:aff></affiliation></author><author><name sortKey="Shim, Jung Min" sort="Shim, Jung Min" uniqKey="Shim J" first="Jung Min" last="Shim">Jung Min Shim</name><affiliation><nlm:aff id="af5-ijms-20-05073">Zoonotic Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jungmin.shim@ip-korea.org</email></nlm:aff></affiliation></author><author><name sortKey="Jin, Jongwha" sort="Jin, Jongwha" uniqKey="Jin J" first="Jongwha" last="Jin">Jongwha Jin</name><affiliation><nlm:aff id="af6-ijms-20-05073">New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea;<email>jichang011@kbiohealth.kr</email> (J.J.);<email>opern88@kbiohealth.kr</email> (C.L.);<email>bettysongyi1@kbiohealth.kr</email> (S.B.)</nlm:aff></affiliation></author><author><name sortKey="Lim, Chungsu" sort="Lim, Chungsu" uniqKey="Lim C" first="Chungsu" last="Lim">Chungsu Lim</name><affiliation><nlm:aff id="af6-ijms-20-05073">New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea;<email>jichang011@kbiohealth.kr</email> (J.J.);<email>opern88@kbiohealth.kr</email> (C.L.);<email>bettysongyi1@kbiohealth.kr</email> (S.B.)</nlm:aff></affiliation></author><author><name sortKey="Baek, Songyi" sort="Baek, Songyi" uniqKey="Baek S" first="Songyi" last="Baek">Songyi Baek</name><affiliation><nlm:aff id="af6-ijms-20-05073">New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea;<email>jichang011@kbiohealth.kr</email> (J.J.);<email>opern88@kbiohealth.kr</email> (C.L.);<email>bettysongyi1@kbiohealth.kr</email> (S.B.)</nlm:aff></affiliation></author><author><name sortKey="Min, Ji Young" sort="Min, Ji Young" uniqKey="Min J" first="Ji-Young" last="Min">Ji-Young Min</name><affiliation><nlm:aff id="af4-ijms-20-05073">Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jinhee.kim@ip-korea.org</email> (J.K.);<email>soyoung.chang@ip-korea.org</email> (S.Y.C.);<email>ji-young.x.min@gsk.com</email> (J.-Y.M.)</nlm:aff></affiliation></author><author><name sortKey="Park, Wan Beom" sort="Park, Wan Beom" uniqKey="Park W" first="Wan Beom" last="Park">Wan Beom Park</name><affiliation><nlm:aff id="af7-ijms-20-05073">Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;<email>wbpark1@snu.ac.kr</email> (W.B.P.);<email>mdohmd@snu.ac.kr</email> (M.-d.O.)</nlm:aff></affiliation></author><author><name sortKey="Oh, Myoung Don" sort="Oh, Myoung Don" uniqKey="Oh M" first="Myoung-Don" last="Oh">Myoung-Don Oh</name><affiliation><nlm:aff id="af7-ijms-20-05073">Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;<email>wbpark1@snu.ac.kr</email> (W.B.P.);<email>mdohmd@snu.ac.kr</email> (M.-d.O.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Seungtaek" sort="Kim, Seungtaek" uniqKey="Kim S" first="Seungtaek" last="Kim">Seungtaek Kim</name><affiliation><nlm:aff id="af5-ijms-20-05073">Zoonotic Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jungmin.shim@ip-korea.org</email></nlm:aff></affiliation></author><author><name sortKey="Chung, Junho" sort="Chung, Junho" uniqKey="Chung J" first="Junho" last="Chung">Junho 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Antibody</title><author><name sortKey="Kim, Sang Il" sort="Kim, Sang Il" uniqKey="Kim S" first="Sang Il" last="Kim">Sang Il Kim</name><affiliation><nlm:aff id="af1-ijms-20-05073">Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea;<email>sangk1128@snu.ac.kr</email> (S.I.K.);<email>sujeong5425@snu.ac.kr</email> (S.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-05073">Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Sujeong" sort="Kim, Sujeong" uniqKey="Kim S" first="Sujeong" last="Kim">Sujeong Kim</name><affiliation><nlm:aff id="af1-ijms-20-05073">Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea;<email>sangk1128@snu.ac.kr</email> (S.I.K.);<email>sujeong5425@snu.ac.kr</email> (S.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-05073">Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name><affiliation><nlm:aff id="af4-ijms-20-05073">Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jinhee.kim@ip-korea.org</email> (J.K.);<email>soyoung.chang@ip-korea.org</email> (S.Y.C.);<email>ji-young.x.min@gsk.com</email> (J.-Y.M.)</nlm:aff></affiliation></author><author><name sortKey="Chang, So Young" sort="Chang, So Young" uniqKey="Chang S" first="So Young" last="Chang">So Young Chang</name><affiliation><nlm:aff id="af4-ijms-20-05073">Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jinhee.kim@ip-korea.org</email> (J.K.);<email>soyoung.chang@ip-korea.org</email> (S.Y.C.);<email>ji-young.x.min@gsk.com</email> (J.-Y.M.)</nlm:aff></affiliation></author><author><name sortKey="Shim, Jung Min" sort="Shim, Jung Min" uniqKey="Shim J" first="Jung Min" last="Shim">Jung Min Shim</name><affiliation><nlm:aff id="af5-ijms-20-05073">Zoonotic Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jungmin.shim@ip-korea.org</email></nlm:aff></affiliation></author><author><name sortKey="Jin, Jongwha" sort="Jin, Jongwha" uniqKey="Jin J" first="Jongwha" last="Jin">Jongwha Jin</name><affiliation><nlm:aff id="af6-ijms-20-05073">New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea;<email>jichang011@kbiohealth.kr</email> (J.J.);<email>opern88@kbiohealth.kr</email> (C.L.);<email>bettysongyi1@kbiohealth.kr</email> (S.B.)</nlm:aff></affiliation></author><author><name sortKey="Lim, Chungsu" sort="Lim, Chungsu" uniqKey="Lim C" first="Chungsu" last="Lim">Chungsu Lim</name><affiliation><nlm:aff id="af6-ijms-20-05073">New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea;<email>jichang011@kbiohealth.kr</email> (J.J.);<email>opern88@kbiohealth.kr</email> (C.L.);<email>bettysongyi1@kbiohealth.kr</email> (S.B.)</nlm:aff></affiliation></author><author><name sortKey="Baek, Songyi" sort="Baek, Songyi" uniqKey="Baek S" first="Songyi" last="Baek">Songyi Baek</name><affiliation><nlm:aff id="af6-ijms-20-05073">New Drug Development Center, 123 Osongsaengmyeng-ro, Cheongju-si, Chungbuk 28160, Korea;<email>jichang011@kbiohealth.kr</email> (J.J.);<email>opern88@kbiohealth.kr</email> (C.L.);<email>bettysongyi1@kbiohealth.kr</email> (S.B.)</nlm:aff></affiliation></author><author><name sortKey="Min, Ji Young" sort="Min, Ji Young" uniqKey="Min J" first="Ji-Young" last="Min">Ji-Young Min</name><affiliation><nlm:aff id="af4-ijms-20-05073">Respiratory Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jinhee.kim@ip-korea.org</email> (J.K.);<email>soyoung.chang@ip-korea.org</email> (S.Y.C.);<email>ji-young.x.min@gsk.com</email> (J.-Y.M.)</nlm:aff></affiliation></author><author><name sortKey="Park, Wan Beom" sort="Park, Wan Beom" uniqKey="Park W" first="Wan Beom" last="Park">Wan Beom Park</name><affiliation><nlm:aff id="af7-ijms-20-05073">Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;<email>wbpark1@snu.ac.kr</email> (W.B.P.);<email>mdohmd@snu.ac.kr</email> (M.-d.O.)</nlm:aff></affiliation></author><author><name sortKey="Oh, Myoung Don" sort="Oh, Myoung Don" uniqKey="Oh M" first="Myoung-Don" last="Oh">Myoung-Don Oh</name><affiliation><nlm:aff id="af7-ijms-20-05073">Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;<email>wbpark1@snu.ac.kr</email> (W.B.P.);<email>mdohmd@snu.ac.kr</email> (M.-d.O.)</nlm:aff></affiliation></author><author><name sortKey="Kim, Seungtaek" sort="Kim, Seungtaek" uniqKey="Kim S" first="Seungtaek" last="Kim">Seungtaek Kim</name><affiliation><nlm:aff id="af5-ijms-20-05073">Zoonotic Virus Laboratory, Institut Pasteur Korea, Gyeonggi-do 13488, Korea;<email>jungmin.shim@ip-korea.org</email></nlm:aff></affiliation></author><author><name sortKey="Chung, Junho" sort="Chung, Junho" uniqKey="Chung J" first="Junho" last="Chung">Junho Chung</name><affiliation><nlm:aff id="af1-ijms-20-05073">Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea;<email>sangk1128@snu.ac.kr</email> (S.I.K.);<email>sujeong5425@snu.ac.kr</email> (S.K.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijms-20-05073">Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijms-20-05073">Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Inhalation</term><term>Animals</term><term>Antibodies, Neutralizing (administration & dosage)</term><term>Antibodies, Neutralizing (genetics)</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (administration & dosage)</term><term>Antibodies, Viral (genetics)</term><term>Antibodies, Viral (immunology)</term><term>Chlorocebus aethiops</term><term>Complementarity Determining Regions (genetics)</term><term>Complementarity Determining Regions (immunology)</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Vero Cells</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Administration par inhalation</term><term>Animaux</term><term>Anticorps antiviraux (administration et posologie)</term><term>Anticorps antiviraux (génétique)</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps neutralisants (administration et posologie)</term><term>Anticorps neutralisants (génétique)</term><term>Anticorps neutralisants (immunologie)</term><term>Cellules Vero</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Humains</term><term>Régions déterminant la complémentarité (génétique)</term><term>Régions déterminant la complémentarité (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Complementarity Determining Regions</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Complementarity Determining Regions</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Régions déterminant la complémentarité</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Régions déterminant la complémentarité</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Inhalation</term><term>Animals</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Administration par inhalation</term><term>Animaux</term><term>Cellules Vero</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. 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Kim</name></author><author><name sortKey="Kim, H" uniqKey="Kim H">H. Kim</name></author><author><name sortKey="Chung, J" uniqKey="Chung J">J. Chung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reed, L J" uniqKey="Reed L">L.J. Reed</name></author><author><name sortKey="Muench, H" uniqKey="Muench H">H. Muench</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><noCountry><name sortKey="Baek, Songyi" sort="Baek, Songyi" uniqKey="Baek S" first="Songyi" last="Baek">Songyi Baek</name><name sortKey="Chang, So Young" sort="Chang, So Young" uniqKey="Chang S" first="So Young" last="Chang">So Young Chang</name><name sortKey="Jin, Jongwha" sort="Jin, Jongwha" uniqKey="Jin J" first="Jongwha" last="Jin">Jongwha Jin</name><name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name><name sortKey="Kim, Seungtaek" sort="Kim, Seungtaek" uniqKey="Kim S" first="Seungtaek" last="Kim">Seungtaek Kim</name><name sortKey="Lim, Chungsu" sort="Lim, Chungsu" uniqKey="Lim C" first="Chungsu" last="Lim">Chungsu Lim</name><name sortKey="Min, Ji Young" sort="Min, Ji Young" uniqKey="Min J" first="Ji-Young" last="Min">Ji-Young Min</name><name sortKey="Oh, Myoung Don" sort="Oh, Myoung Don" uniqKey="Oh M" first="Myoung-Don" last="Oh">Myoung-Don Oh</name><name sortKey="Park, Wan Beom" sort="Park, Wan Beom" uniqKey="Park W" first="Wan Beom" last="Park">Wan Beom Park</name><name sortKey="Shim, Jung Min" sort="Shim, Jung Min" uniqKey="Shim J" first="Jung Min" last="Shim">Jung Min Shim</name></noCountry><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Sang Il" sort="Kim, Sang Il" uniqKey="Kim S" first="Sang Il" last="Kim">Sang Il Kim</name></region><name sortKey="Chung, Junho" sort="Chung, Junho" uniqKey="Chung J" first="Junho" last="Chung">Junho Chung</name><name sortKey="Chung, Junho" sort="Chung, Junho" uniqKey="Chung J" first="Junho" last="Chung">Junho Chung</name><name sortKey="Kim, Sujeong" sort="Kim, Sujeong" uniqKey="Kim S" first="Sujeong" last="Kim">Sujeong Kim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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