Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition
Identifieur interne : 001803 ( Istex/Corpus ); précédent : 001802; suivant : 001804Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition
Auteurs : M. J. Edwards ; N. J. DimmockSource :
- Virology [ 0042-6822 ] ; 2000.
English descriptors
- KwdEn :
- Teeft :
- Academic press, Antibody concentration, Antibody fragments, Antibody isotype, Antigenic, Antigenic site, Antigenic sites, Assay, Attachment, Attachment inhibition, Biol, Cell biol, Cold dmem, Colloidal coomassie, Dimmock, Dmem, Elisa, Epitope, Fabs, Fluorescence dequenching, Functional affinities, Fusion, Fusion activity, Fusion inhibition, Fusion process, Gerhard, Gibco, Higher concentration, Igg, Igg2a, Igg3, Infectivity, Influenza, Influenza virus, Inhibition, Internalization, Mabs, Mdck, Mdck cells, Monolayers, Neuraminidase, Neutralization, Neutralization activity, Neutralizing, Nonlinear regression analysis, Partial inhibition, Percentage attachment, Percentage infectivity, Receptor, Same batch, Same mixtures, Same system, Same time, Schofield, Sigma, Similar data, Simple neutralization, Surface plasmon resonance, Target cell, Target cells, Virion, Virol, Virology, Virus, Virus attachment, Virus control, Virus controls, Virus fusion, Virus internalization, Warm dmem.
Abstract
Abstract: Mabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.
Url:
DOI: 10.1006/viro.2000.0631
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ISTEX:1AEBEC4A096C908436AE669C5225D8BC0E765AE8Le document en format XML
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Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>dimmock</json:string><json:string>fabs</json:string><json:string>neutralization</json:string><json:string>infectivity</json:string><json:string>mdck</json:string><json:string>igg</json:string><json:string>virus attachment</json:string><json:string>monolayers</json:string><json:string>internalization</json:string><json:string>neutralizing</json:string><json:string>influenza virus</json:string><json:string>antigenic</json:string><json:string>target cells</json:string><json:string>elisa</json:string><json:string>virol</json:string><json:string>virion</json:string><json:string>epitope</json:string><json:string>mabs</json:string><json:string>influenza</json:string><json:string>schofield</json:string><json:string>target cell</json:string><json:string>assay</json:string><json:string>virology</json:string><json:string>neuraminidase</json:string><json:string>igg2a</json:string><json:string>dmem</json:string><json:string>biol</json:string><json:string>attachment inhibition</json:string><json:string>gibco</json:string><json:string>same system</json:string><json:string>igg3</json:string><json:string>receptor</json:string><json:string>mdck cells</json:string><json:string>percentage infectivity</json:string><json:string>virus</json:string><json:string>attachment</json:string><json:string>fusion inhibition</json:string><json:string>fusion activity</json:string><json:string>sigma</json:string><json:string>inhibition</json:string><json:string>virus controls</json:string><json:string>antigenic site</json:string><json:string>percentage attachment</json:string><json:string>partial inhibition</json:string><json:string>cold dmem</json:string><json:string>fluorescence dequenching</json:string><json:string>neutralization activity</json:string><json:string>simple neutralization</json:string><json:string>functional affinities</json:string><json:string>academic press</json:string><json:string>virus fusion</json:string><json:string>gerhard</json:string><json:string>same mixtures</json:string><json:string>virus internalization</json:string><json:string>antibody isotype</json:string><json:string>nonlinear regression analysis</json:string><json:string>similar data</json:string><json:string>surface plasmon resonance</json:string><json:string>virus control</json:string><json:string>fusion process</json:string><json:string>higher concentration</json:string><json:string>antigenic sites</json:string><json:string>antibody fragments</json:string><json:string>colloidal coomassie</json:string><json:string>warm dmem</json:string><json:string>antibody concentration</json:string><json:string>same time</json:string><json:string>same batch</json:string><json:string>cell biol</json:string><json:string>fusion</json:string></teeft></keywords><author><json:item><name>M.J. Edwards</name><affiliations><json:string>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</json:string></affiliations></json:item><json:item><name>N.J. Dimmock</name><affiliations><json:string>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>influenza A virus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neutralization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IgG</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Fab</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>F(ab′)2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>affinity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mechanism of neutralization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>inhibition of attachment</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>inhibition of internalization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>inhibition of fusion</value></json:item></subject><arkIstex>ark:/67375/6H6-ST2T208D-K</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Mabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.</abstract><qualityIndicators><score>10</score><pdfWordCount>8216</pdfWordCount><pdfCharCount>48991</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>13</pdfPageCount><pdfPageSize>536 x 722 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>269</abstractWordCount><abstractCharCount>1880</abstractCharCount><keywordCount>10</keywordCount></qualityIndicators><title>Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition</title><pmid><json:string>11118365</json:string></pmid><pii><json:string>S0042-6822(00)90631-7</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Virology</title><language><json:string>unknown</json:string></language><publicationDate>2000</publicationDate><issn><json:string>0042-6822</json:string></issn><pii><json:string>S0042-6822(00)X0029-3</json:string></pii><volume>278</volume><issue>2</issue><pages><first>423</first><last>435</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2000</json:string></date><geogName></geogName><orgName><json:string>Dako</json:string><json:string>GibcoBRL Life Technologies, Paisley, UK</json:string><json:string>UK</json:string><json:string>Sigma</json:string><json:string>Novabiochem</json:string><json:string>Edward Jenner Institute for Vaccine Research, Compton RG</json:string><json:string>Wistar Institute, Philadelphia, PA</json:string><json:string>Serotech</json:string><json:string>Life Sciences International</json:string><json:string>Jude Children’s Research Hospital, Memphis, TN</json:string><json:string>Calbiochem</json:string><json:string>United Kingdom Received</json:string><json:string>University of Reading, UK</json:string><json:string>Blood Institute</json:string><json:string>National Heart</json:string><json:string>Lung</json:string><json:string>NIH</json:string></orgName><orgName_funder><json:string>Blood Institute</json:string><json:string>National Heart</json:string><json:string>Lung</json:string><json:string>NIH</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>IgG</json:string><json:string>A. C. Marriott</json:string><json:string>C. Parry</json:string><json:string>Fab</json:string><json:string>Walter Gerhard</json:string><json:string>N. J. Dimmock</json:string><json:string>Data</json:string><json:string>Wendy Barclay</json:string><json:string>To</json:string><json:string>Gerhard</json:string><json:string>Ian Campbell</json:string><json:string>Robert G. Webster</json:string></persName><placeName><json:string>Leiden</json:string><json:string>Milton Keynes</json:string><json:string>Poole</json:string><json:string>Puerto Rico</json:string><json:string>Europe</json:string><json:string>Ely</json:string><json:string>Netherlands</json:string></placeName><ref_url><json:string>http://www.idealibrary.com</json:string></ref_url><ref_bibl><json:string>Schofield et al., 1997a</json:string><json:string>Haddad and Hutt-Fletcher, 1989</json:string><json:string>Caton et al. (1982)</json:string><json:string>Lamarre and Talbot, 1995</json:string><json:string>McInerney et al., 1997</json:string><json:string>Dimmock, 1993</json:string><json:string>Matlin et al., 1981</json:string><json:string>Stewart et al., 1997</json:string><json:string>Horling et al., 1992</json:string><json:string>Kingsford et al., 1991</json:string><json:string>Possee et al., 1982</json:string><json:string>Tsurudome et al., 1992</json:string><json:string>Outlaw and Dimmock, 1993</json:string><json:string>Armstrong and Dimmock, 1992</json:string><json:string>Miller and Hutt-Fletcher, 1988</json:string><json:string>Stegmann et al., 1987</json:string><json:string>Richman et al., 1986</json:string><json:string>Hernandez et al., 1996</json:string><json:string>Outlaw and Dimmock, 1990, 1993</json:string><json:string>Ugolini et al., 1997</json:string><json:string>Lafferty, 1963</json:string><json:string>Ghendon, 1990</json:string><json:string>Harlow and Lane, 1988</json:string><json:string>Schofield and Dimmock, 1996</json:string><json:string>Daukas and Zigmond, 1985</json:string><json:string>Bullough et al., 1994</json:string><json:string>Palokangas et al., 1994</json:string><json:string>Wrigley et al., 1977, 1983</json:string><json:string>Possee and Dimmock, 1981</json:string><json:string>Blumenthal et al., 1987</json:string><json:string>Heuser and Anderson, 1989</json:string><json:string>Centers for Disease Control and Prevention, 1998</json:string><json:string>Wiley et al. (1981)</json:string><json:string>Webster, 1998</json:string><json:string>Kida et al., 1985</json:string><json:string>Outlaw et al., 1990</json:string><json:string>Schofield et al. (1997b)</json:string><json:string>Outlaw and Dimmock, 1990</json:string><json:string>Caton et al., 1982</json:string><json:string>Hudson and Hay, 1989</json:string><json:string>Dimmock et al., 1984</json:string><json:string>Ochiai et al., 1995</json:string><json:string>Rigg et al., 1989</json:string><json:string>Schofield et al., 1997b</json:string><json:string>Staudt and Gerhard, 1983</json:string><json:string>Yoden et al., 1986</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-ST2T208D-K</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - virology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - virology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Virology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences biologiques fondamentales et appliquees. psychologie</json:string><json:string>4 - agronomie. sciences du sol et productions vegetales</json:string></inist></categories><publicationDate>2000</publicationDate><copyrightDate>2000</copyrightDate><doi><json:string>10.1006/viro.2000.0631</json:string></doi><id>1AEBEC4A096C908436AE669C5225D8BC0E765AE8</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ST2T208D-K/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ST2T208D-K/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-ST2T208D-K/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©2000 Academic Press</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>2000</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Section title: Regular Article</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition</title><author xml:id="author-0000"><persName><forename type="first">M.J.</forename><surname>Edwards</surname></persName><note type="biography">Present address: The Edward Jenner Institute for Vaccine Research, Compton RG20 7NN, UK.</note><affiliation>Present address: The Edward Jenner Institute for Vaccine Research, Compton RG20 7NN, UK.</affiliation><affiliation>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</affiliation></author><author xml:id="author-0001"><persName><forename type="first">N.J.</forename><surname>Dimmock</surname></persName><affiliation>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</affiliation></author><idno type="istex">1AEBEC4A096C908436AE669C5225D8BC0E765AE8</idno><idno type="ark">ark:/67375/6H6-ST2T208D-K</idno><idno type="DOI">10.1006/viro.2000.0631</idno><idno type="PII">S0042-6822(00)90631-7</idno></analytic><monogr><title level="j">Virology</title><title level="j" type="abbrev">YVIRO</title><idno type="pISSN">0042-6822</idno><idno type="PII">S0042-6822(00)X0029-3</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000"></date><biblScope unit="volume">278</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="423">423</biblScope><biblScope unit="page" to="435">435</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Mabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>influenza A virus</term></item><item><term>neutralization</term></item><item><term>IgG</term></item><item><term>Fab</term></item><item><term>F(ab′)2</term></item><item><term>affinity</term></item><item><term>mechanism of neutralization</term></item><item><term>inhibition of attachment</term></item><item><term>inhibition of internalization</term></item><item><term>inhibition of fusion</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2000-06-01">Modified</change><change when="2000">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ST2T208D-K/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>YVIRO</jid><aid>90631</aid><ce:pii>S0042-6822(00)90631-7</ce:pii><ce:doi>10.1006/viro.2000.0631</ce:doi><ce:copyright type="full-transfer" year="2000">Academic Press</ce:copyright></item-info><head><ce:dochead><ce:textfn>Regular Article</ce:textfn></ce:dochead><ce:title>Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition</ce:title><ce:author-group><ce:author><ce:given-name>M.J.</ce:given-name><ce:surname>Edwards</ce:surname><ce:cross-ref refid="FN1"><ce:sup>1</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>N.J.</ce:given-name><ce:surname>Dimmock</ce:surname><ce:cross-ref refid="FN2"><ce:sup>2</ce:sup></ce:cross-ref></ce:author><ce:affiliation><ce:textfn>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</ce:textfn></ce:affiliation><ce:footnote id="FN1"><ce:label>1</ce:label><ce:note-para>Present address: The Edward Jenner Institute for Vaccine Research, Compton RG20 7NN, UK.</ce:note-para></ce:footnote><ce:footnote id="FN2"><ce:label>2</ce:label><ce:note-para>To whom correspondence and reprint requests should be addressed. Fax: +44 1 2476 523593. E-mail: ndimmock@bio.warwick.ac.uk.</ce:note-para></ce:footnote></ce:author-group><ce:date-received day="25" month="4" year="2000"></ce:date-received><ce:date-revised day="1" month="6" year="2000"></ce:date-revised><ce:date-accepted day="7" month="9" year="2000"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Mabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)<ce:inf>2</ce:inf> resembled that for IgG, although eightfold more F(ab′)<ce:inf>2</ce:inf> was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>influenza A virus</ce:text></ce:keyword><ce:keyword><ce:text>neutralization</ce:text></ce:keyword><ce:keyword><ce:text>IgG</ce:text></ce:keyword><ce:keyword><ce:text>Fab</ce:text></ce:keyword><ce:keyword><ce:text>F(ab′)<ce:inf>2</ce:inf></ce:text></ce:keyword><ce:keyword><ce:text>affinity</ce:text></ce:keyword><ce:keyword><ce:text>mechanism of neutralization</ce:text></ce:keyword><ce:keyword><ce:text>inhibition of attachment</ce:text></ce:keyword><ce:keyword><ce:text>inhibition of internalization</ce:text></ce:keyword><ce:keyword><ce:text>inhibition of fusion</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition</title></titleInfo><name type="personal"><namePart type="given">M.J.</namePart><namePart type="family">Edwards</namePart><affiliation>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</affiliation><description>Present address: The Edward Jenner Institute for Vaccine Research, Compton RG20 7NN, UK.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">N.J.</namePart><namePart type="family">Dimmock</namePart><affiliation>Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom</affiliation><description>To whom correspondence and reprint requests should be addressed. Fax: +44 1 2476 523593. E-mail: ndimmock@bio.warwick.ac.uk.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued><dateModified encoding="w3cdtf">2000-06-01</dateModified><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Mabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.</abstract><note type="content">Section title: Regular Article</note><subject lang="en"><genre>Keywords</genre><topic>influenza A virus</topic><topic>neutralization</topic><topic>IgG</topic><topic>Fab</topic><topic>F(ab′)2</topic><topic>affinity</topic><topic>mechanism of neutralization</topic><topic>inhibition of attachment</topic><topic>inhibition of internalization</topic><topic>inhibition of fusion</topic></subject><relatedItem type="host"><titleInfo><title>Virology</title></titleInfo><titleInfo type="abbreviated"><title>YVIRO</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued></originInfo><identifier type="ISSN">0042-6822</identifier><identifier type="PII">S0042-6822(00)X0029-3</identifier><part><date>2000</date><detail type="volume"><number>278</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue-pages"><start>301</start><end>623</end></extent><extent unit="pages"><start>423</start><end>435</end></extent></part></relatedItem><identifier type="istex">1AEBEC4A096C908436AE669C5225D8BC0E765AE8</identifier><identifier type="ark">ark:/67375/6H6-ST2T208D-K</identifier><identifier type="DOI">10.1006/viro.2000.0631</identifier><identifier type="PII">S0042-6822(00)90631-7</identifier><accessCondition type="use and reproduction" contentType="copyright">©2000 Academic Press</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Academic Press, ©2000</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ST2T208D-K/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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