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Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1

Identifieur interne : 000401 ( Istex/Corpus ); précédent : 000400; suivant : 000402

Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1

Auteurs : A. Ebersold ; V. Boyer ; P. J. Klasse ; M. Holnigue ; C. Fraisier ; J. M. Cocchi ; R. Pipkorn ; J. Blomberg ; C. Desgranges

Source :

RBID : ISTEX:D485D531AA1B2F6D22431C4A22EFCE818A012DEF

English descriptors

Abstract

Summary: Human spleen cells from an HIV-seropositive donor were immunized in vitro with the aa583–599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583–599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583–599 octopus-lysconjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20 μg/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583–599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.
Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés in vitro par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH2-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.

Url:
DOI: 10.1016/S0923-2516(06)80102-0

Links to Exploration step

ISTEX:D485D531AA1B2F6D22431C4A22EFCE818A012DEF

Le document en format XML

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<div type="abstract" xml:lang="en">Summary: Human spleen cells from an HIV-seropositive donor were immunized in vitro with the aa583–599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583–599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583–599 octopus-lysconjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20 μg/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583–599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.</div>
<div type="abstract" xml:lang="fr">Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés in vitro par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH2-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.</div>
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<p>Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés in vitro par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH2-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.</p>
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<ce:title>Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1</ce:title>
<ce:alt-title xml:lang="fr">Anticorps monoclonaux humain et murin dirigés contre une séquence conservée de la gp41 (aa583-599) du virus de l'immunodéficience humaine</ce:alt-title>
<ce:author-group>
<ce:author>
<ce:given-name>A.</ce:given-name>
<ce:surname>Ebersold</ce:surname>
<ce:cross-ref refid="aff1">
<ce:sup>(1)</ce:sup>
</ce:cross-ref>
<ce:cross-ref refid="cor1">
<ce:sup>(*)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>V.</ce:given-name>
<ce:surname>Boyer</ce:surname>
<ce:cross-ref refid="aff1">
<ce:sup>(1)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>P.J.</ce:given-name>
<ce:surname>Klasse</ce:surname>
<ce:cross-ref refid="aff2">
<ce:sup>(2)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>M.</ce:given-name>
<ce:surname>Holnigue</ce:surname>
<ce:cross-ref refid="aff3">
<ce:sup>(3)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>C.</ce:given-name>
<ce:surname>Fraisier</ce:surname>
<ce:cross-ref refid="aff1">
<ce:sup>(1)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>J.M.</ce:given-name>
<ce:surname>Cocchi</ce:surname>
<ce:cross-ref refid="aff1">
<ce:sup>(1)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>R.</ce:given-name>
<ce:surname>Pipkorn</ce:surname>
<ce:cross-ref refid="aff4">
<ce:sup>(4)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>J.</ce:given-name>
<ce:surname>Blomberg</ce:surname>
<ce:cross-ref refid="aff2">
<ce:sup>(2)</ce:sup>
</ce:cross-ref>
</ce:author>
<ce:author>
<ce:given-name>C.</ce:given-name>
<ce:surname>Desgranges</ce:surname>
<ce:cross-ref refid="aff1">
<ce:sup>(1)</ce:sup>
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</ce:affiliation>
<ce:affiliation id="aff2">
<ce:label>(2)</ce:label>
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</ce:affiliation>
<ce:affiliation id="aff3">
<ce:label>(3)</ce:label>
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</ce:affiliation>
<ce:affiliation id="aff4">
<ce:label>(4)</ce:label>
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<ce:date-received day="5" month="2" year="1992"></ce:date-received>
<ce:date-accepted day="24" month="4" year="1992"></ce:date-accepted>
<ce:abstract id="ab1" class="author" xml:lang="en">
<ce:section-title>Summary</ce:section-title>
<ce:abstract-sec>
<ce:simple-para>Human spleen cells from an HIV-seropositive donor were immunized
<ce:italic>in vitro</ce:italic>
with the aa583–599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583–599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583–599 octopus-lysconjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20 μg/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583–599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.</ce:simple-para>
</ce:abstract-sec>
</ce:abstract>
<ce:abstract id="ab2" class="author" xml:lang="fr">
<ce:abstract-sec>
<ce:simple-para>Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés
<ce:italic>in vitro</ce:italic>
par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH
<ce:inf loc="post">2</ce:inf>
-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.</ce:simple-para>
</ce:abstract-sec>
</ce:abstract>
<ce:keywords class="keyword" xml:lang="en">
<ce:section-title>Key-words</ce:section-title>
<ce:keyword>
<ce:text>Lymphocyte, Peptide, HIV, AIDS, mAb, IgM, Immunotherapy</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>gp41, Immunosuppression, Syncytia, pHIVIS, Heptalysine</ce:text>
</ce:keyword>
</ce:keywords>
<ce:keywords class="keyword" xml:lang="fr">
<ce:section-title>Mots-clés</ce:section-title>
<ce:keyword>
<ce:text>Lymphocyte, HIV, Peptide, Anticorps monoclonal, IgM, VIH1, SIDA, Immunothérapie</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>gp41, Immunosuppression, Syncytia, pHIVIS, Heptalysine</ce:text>
</ce:keyword>
</ce:keywords>
</head>
<tail>
<ce:bibliography>
<ce:section-title>References</ce:section-title>
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<ce:label>Borrebaeck, et al, 1988</ce:label>
<sb:reference>
<sb:contribution langtype="en">
<sb:authors>
<sb:author>
<ce:surname>Borrebaeck</ce:surname>
<ce:given-name>C.A.K.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Danielsson</ce:surname>
<ce:given-name>L.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Möller</ce:surname>
<ce:given-name>S.A.</ce:given-name>
</sb:author>
</sb:authors>
<sb:title>
<sb:maintitle>Human monoclonal antibodies produced by primary
<ce:italic>in vitro</ce:italic>
immunization of peripheral blood lymphocytes</sb:maintitle>
</sb:title>
</sb:contribution>
<sb:host>
<sb:edited-book>
<sb:book-series>
<sb:series>
<sb:title>
<sb:maintitle>Proc. nat. Acad. Sci. (Wash.)</sb:maintitle>
</sb:title>
<sb:volume-nr>85</sb:volume-nr>
</sb:series>
</sb:book-series>
<sb:date>1988</sb:date>
</sb:edited-book>
<sb:pages>
<sb:first-page>3995</sb:first-page>
</sb:pages>
</sb:host>
</sb:reference>
</ce:bib-reference>
<ce:bib-reference id="bib2">
<ce:label>Boyer, et al, 1991</ce:label>
<sb:reference>
<sb:contribution langtype="en">
<sb:authors>
<sb:author>
<ce:surname>Boyer</ce:surname>
<ce:given-name>V.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Broly</ce:surname>
<ce:given-name>H.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Souche</ce:surname>
<ce:given-name>S.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Madaule</ce:surname>
<ce:given-name>P.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Rossier</ce:surname>
<ce:given-name>J.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Zagury</ce:surname>
<ce:given-name>D.</ce:given-name>
</sb:author>
<sb:author>
<ce:surname>Desgranges</ce:surname>
<ce:given-name>C.</ce:given-name>
</sb:author>
</sb:authors>
<sb:title>
<sb:maintitle>Characterization and large production of human monoclonal antibodies against the HIV-1 envelope</sb:maintitle>
</sb:title>
</sb:contribution>
<sb:host>
<sb:issue>
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<title>Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1</title>
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<title>Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1</title>
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<titleInfo type="translated" lang="fr">
<title>Anticorps monoclonaux humain et murin dirigés contre une séquence conservée de la gp41 (aa583-599) du virus de l'immunodéficience humaine</title>
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<name type="personal">
<namePart type="given">A.</namePart>
<namePart type="family">Ebersold</namePart>
<affiliation>Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus humains, INSERM U271, 151 Cours Albert Thomas, 69424 Lyon Cedex 03 (France)</affiliation>
<affiliation>Corresponding author.</affiliation>
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</role>
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<name type="personal">
<namePart type="given">V.</namePart>
<namePart type="family">Boyer</namePart>
<affiliation>Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus humains, INSERM U271, 151 Cours Albert Thomas, 69424 Lyon Cedex 03 (France)</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
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<name type="personal">
<namePart type="given">P.J.</namePart>
<namePart type="family">Klasse</namePart>
<affiliation>Section of Virology, Lund University, Lund (Sweden)</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">M.</namePart>
<namePart type="family">Holnigue</namePart>
<affiliation>Centre Régional de Transfusion sanguine, 59000 Lille (France)</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">C.</namePart>
<namePart type="family">Fraisier</namePart>
<affiliation>Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus humains, INSERM U271, 151 Cours Albert Thomas, 69424 Lyon Cedex 03 (France)</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
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<name type="personal">
<namePart type="given">J.M.</namePart>
<namePart type="family">Cocchi</namePart>
<affiliation>Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus humains, INSERM U271, 151 Cours Albert Thomas, 69424 Lyon Cedex 03 (France)</affiliation>
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<roleTerm type="text">author</roleTerm>
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<name type="personal">
<namePart type="given">R.</namePart>
<namePart type="family">Pipkorn</namePart>
<affiliation>Novabiochem AG, Sandhausen, Heidelberg (Germany)</affiliation>
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<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">J.</namePart>
<namePart type="family">Blomberg</namePart>
<affiliation>Section of Virology, Lund University, Lund (Sweden)</affiliation>
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<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">C.</namePart>
<namePart type="family">Desgranges</namePart>
<affiliation>Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus humains, INSERM U271, 151 Cours Albert Thomas, 69424 Lyon Cedex 03 (France)</affiliation>
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<publisher>ELSEVIER</publisher>
<dateIssued encoding="w3cdtf">1992</dateIssued>
<copyrightDate encoding="w3cdtf">1992</copyrightDate>
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<abstract lang="en">Summary: Human spleen cells from an HIV-seropositive donor were immunized in vitro with the aa583–599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583–599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583–599 octopus-lysconjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20 μg/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583–599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.</abstract>
<abstract lang="fr">Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés in vitro par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH2-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.</abstract>
<subject lang="en">
<genre>Key-words</genre>
<topic>Lymphocyte, Peptide, HIV, AIDS, mAb, IgM, Immunotherapy</topic>
<topic>gp41, Immunosuppression, Syncytia, pHIVIS, Heptalysine</topic>
</subject>
<subject lang="fr">
<genre>Mots-clés</genre>
<topic>Lymphocyte, HIV, Peptide, Anticorps monoclonal, IgM, VIH1, SIDA, Immunothérapie</topic>
<topic>gp41, Immunosuppression, Syncytia, pHIVIS, Heptalysine</topic>
</subject>
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<dateIssued encoding="w3cdtf">1992</dateIssued>
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<identifier type="ISSN">0923-2516</identifier>
<identifier type="PII">S0923-2516(06)X8065-2</identifier>
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<date>1992</date>
<detail type="volume">
<number>143</number>
<caption>vol.</caption>
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<accessCondition type="use and reproduction" contentType="copyright">©1992 Éditions Scientifiques Elsevier, Paris</accessCondition>
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