Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody
Identifieur interne : 003216 ( Main/Exploration ); précédent : 003215; suivant : 003217Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody
Auteurs : Zhongyu Zhu [États-Unis] ; Katharine N. Bossart [Australie] ; Kimberly A. Bishop ; Gary Crameri [Australie] ; Antony S. Dimitrov ; Jennifer A. Mceachern [Australie] ; Yang Feng ; Deborah Middleton [Australie] ; Lin-Fa Wang [Australie] ; Christopher C. Broder ; Dimiter S. DimitrovSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2008.
Abstract
We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sGHeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sGHeV. One of the selected antibody Fab clones, m102.4, had affinity of binding to sGHeV that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sGHeV and sGNiV. m102.4 bound a soluble form of NiV G (sGNiV) better than it bound sGHeV, and it neutralized NiV better than HeV, despite being originally selected against sGHeV. These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent
Url:
DOI: 10.1086/528801
Affiliations:
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Dimitrov, Protein Interactions Group, CCRNP, NCI-Frederick, NIH, Bldg. 469, Rm. 150B, PO Box B, Miller Dr., Frederick</wicri:cityArea></affiliation></author><author wicri:is="90%"><name sortKey="Bossart, Katharine N" sort="Bossart, Katharine N" uniqKey="Bossart K" first="Katharine N" last="Bossart">Katharine N. Bossart</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Commonwealth Scientific and Industrial Research Organization Livestock Industries, Australian Animal Health Laboratory and Australian Biosecurity Cooperative Research Center for Emerging Infectious DiseasesGeelong, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author wicri:is="90%"><name sortKey="Bishop, Kimberly A" sort="Bishop, Kimberly A" uniqKey="Bishop K" first="Kimberly A" last="Bishop">Kimberly A. 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Broder</name><affiliation><wicri:noCountry code="subField">Maryland;</wicri:noCountry></affiliation></author><author wicri:is="90%"><name sortKey="Dimitrov, Dimiter S" sort="Dimitrov, Dimiter S" uniqKey="Dimitrov D" first="Dimiter S" last="Dimitrov">Dimiter S. Dimitrov</name><affiliation><wicri:noCountry code="subField">Health</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published">2008</date><biblScope unit="vol">197</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="846">846</biblScope><biblScope unit="page" to="853">853</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sGHeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sGHeV. One of the selected antibody Fab clones, m102.4, had affinity of binding to sGHeV that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sGHeV and sGNiV. m102.4 bound a soluble form of NiV G (sGNiV) better than it bound sGHeV, and it neutralized NiV better than HeV, despite being originally selected against sGHeV. These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent</div></front></TEI><affiliations><list><country><li>Australie</li><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Bishop, Kimberly A" sort="Bishop, Kimberly A" uniqKey="Bishop K" first="Kimberly A" last="Bishop">Kimberly A. Bishop</name><name sortKey="Broder, Christopher C" sort="Broder, Christopher C" uniqKey="Broder C" first="Christopher C" last="Broder">Christopher C. Broder</name><name sortKey="Dimitrov, Antony S" sort="Dimitrov, Antony S" uniqKey="Dimitrov A" first="Antony S" last="Dimitrov">Antony S. Dimitrov</name><name sortKey="Dimitrov, Dimiter S" sort="Dimitrov, Dimiter S" uniqKey="Dimitrov D" first="Dimiter S" last="Dimitrov">Dimiter S. Dimitrov</name><name sortKey="Feng, Yang" sort="Feng, Yang" uniqKey="Feng Y" first="Yang" last="Feng">Yang Feng</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Zhu, Zhongyu" sort="Zhu, Zhongyu" uniqKey="Zhu Z" first="Zhongyu" last="Zhu">Zhongyu Zhu</name></region></country><country name="Australie"><noRegion><name sortKey="Bossart, Katharine N" sort="Bossart, Katharine N" uniqKey="Bossart K" first="Katharine N" last="Bossart">Katharine N. Bossart</name></noRegion><name sortKey="Crameri, Gary" sort="Crameri, Gary" uniqKey="Crameri G" first="Gary" last="Crameri">Gary Crameri</name><name sortKey="Mceachern, Jennifer A" sort="Mceachern, Jennifer A" uniqKey="Mceachern J" first="Jennifer A" last="Mceachern">Jennifer A. Mceachern</name><name sortKey="Middleton, Deborah" sort="Middleton, Deborah" uniqKey="Middleton D" first="Deborah" last="Middleton">Deborah Middleton</name><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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