Chimerization and characterization of a monoclonal antibody with potent neutralizing activity across multiple influenza A H5N1 clades
Identifieur interne : 001120 ( Main/Exploration ); précédent : 001119; suivant : 001121Chimerization and characterization of a monoclonal antibody with potent neutralizing activity across multiple influenza A H5N1 clades
Auteurs : Tze-Minn Mak [Singapour] ; Brendon J. Hanson [Singapour] ; Yee-Joo Tan [Singapour]Source :
- Antiviral research [ 0166-3542 ] ; 2014.
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- Pascal (Inist)
English descriptors
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Abstract
The persistent evolution and circulation of highly pathogenic avian influenza H5N1 viruses pose a serious threat to global heath and hamper pandemic preparedness through conventional vaccine strategies. Combination passive immunotherapy using non-competing neutralizing antibodies has been proposed as a viable alternative to provide broad protection against drift variants. This necessitates the pre-pandemic production and characterization of potently neutralizing monoclonal antibodies (MAbs). One such antibody, MAb 9F4 was shown to provide heterologous protection against multiple H5N1 clade viruses, including one of the recently designated subclades, namely 2.3.4, through binding to a novel epitope, warranting its further development and characterization as a therapeutic candidate. In this study, the conversion of MAb 9F4 from mouse IgG2b to mouse-human chimeric (xi) IgG1 and IgA1 was achieved. These chimeric MAb versions were found to retain high degrees of binding and neutralizing activity against H5N1. The demonstration that xi-IgA1-9F4 retains a fairly high level of neutralizing activity, which is ˜10-fold lower than the corresponding xi-IgG1 isotype, suggests that this MAb could be further developed and engineered for intranasal administration.
Affiliations:
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Hanson</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Defence Medical and Environmental Research Institute, DSO National Laboratories</s1><s3>SGP</s3><sZ>2 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Defence Medical and Environmental Research Institute, DSO National Laboratories</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Infrastructure, Technology and Translational Division, Institute of Molecular and Cell Biology, A*STAR</s1><s3>SGP</s3><sZ>3 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Infrastructure, Technology and Translational Division, Institute of Molecular and Cell Biology, A*STAR</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore</s1><s3>SGP</s3><sZ>3 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0168547</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0168547 INIST</idno><idno type="RBID">Pascal:14-0168547</idno><idno type="wicri:Area/PascalFrancis/Corpus">000079</idno><idno type="wicri:Area/PascalFrancis/Curation">001D40</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000129</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000129</idno><idno type="wicri:doubleKey">0166-3542:2014:Mak T:chimerization:and:characterization</idno><idno type="wicri:Area/Main/Merge">001130</idno><idno type="wicri:Area/Main/Curation">001120</idno><idno type="wicri:Area/Main/Exploration">001120</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Chimerization and characterization of a monoclonal antibody with potent neutralizing activity across multiple influenza A H5N1 clades</title><author><name sortKey="Mak, Tze Minn" sort="Mak, Tze Minn" uniqKey="Mak T" first="Tze-Minn" last="Mak">Tze-Minn Mak</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore</s1><s3>SGP</s3><sZ>1 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Hanson, Brendon J" sort="Hanson, Brendon J" uniqKey="Hanson B" first="Brendon J." last="Hanson">Brendon J. Hanson</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Defence Medical and Environmental Research Institute, DSO National Laboratories</s1><s3>SGP</s3><sZ>2 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Defence Medical and Environmental Research Institute, DSO National Laboratories</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Infrastructure, Technology and Translational Division, Institute of Molecular and Cell Biology, A*STAR</s1><s3>SGP</s3><sZ>3 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Infrastructure, Technology and Translational Division, Institute of Molecular and Cell Biology, A*STAR</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore</s1><s3>SGP</s3><sZ>3 aut.</sZ></inist:fA14><country>Singapour</country><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></analytic><series><title level="j" type="main">Antiviral research</title><title level="j" type="abbreviated">Antivir. res.</title><idno type="ISSN">0166-3542</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Antiviral research</title><title level="j" type="abbreviated">Antivir. res.</title><idno type="ISSN">0166-3542</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Characterization</term><term>Hemagglutinin</term><term>Influenza</term><term>Influenzavirus A(H5N1)</term><term>Monoclonal antibody</term><term>Multiple</term><term>Neutralization</term><term>Neutralizing antibody</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Caractérisation</term><term>Anticorps monoclonal</term><term>Multiple</term><term>Grippe</term><term>Anticorps neutralisant</term><term>Neutralisation</term><term>Hémagglutinine</term><term>Influenzavirus A(H5N1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The persistent evolution and circulation of highly pathogenic avian influenza H5N1 viruses pose a serious threat to global heath and hamper pandemic preparedness through conventional vaccine strategies. Combination passive immunotherapy using non-competing neutralizing antibodies has been proposed as a viable alternative to provide broad protection against drift variants. This necessitates the pre-pandemic production and characterization of potently neutralizing monoclonal antibodies (MAbs). One such antibody, MAb 9F4 was shown to provide heterologous protection against multiple H5N1 clade viruses, including one of the recently designated subclades, namely 2.3.4, through binding to a novel epitope, warranting its further development and characterization as a therapeutic candidate. In this study, the conversion of MAb 9F4 from mouse IgG<sub>2b</sub> to mouse-human chimeric (xi) IgG<sub>1</sub> and IgA<sub>1</sub> was achieved. These chimeric MAb versions were found to retain high degrees of binding and neutralizing activity against H5N1. The demonstration that xi-IgA<sub>1</sub>-9F4 retains a fairly high level of neutralizing activity, which is ˜10-fold lower than the corresponding xi-IgG<sub>1</sub> isotype, suggests that this MAb could be further developed and engineered for intranasal administration.</div></front></TEI><affiliations><list><country><li>Singapour</li></country><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Mak, Tze Minn" sort="Mak, Tze Minn" uniqKey="Mak T" first="Tze-Minn" last="Mak">Tze-Minn Mak</name></noRegion><name sortKey="Hanson, Brendon J" sort="Hanson, Brendon J" uniqKey="Hanson B" first="Brendon J." last="Hanson">Brendon J. Hanson</name><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name><name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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