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Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120
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Zeitschriftentitel: | Journal of Virology |
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Personen und Körperschaften: | , , , , , , , , , |
In: | Journal of Virology, 87, 2013, 2, S. 1137-1149 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society for Microbiology
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Schlagwörter: |
author_facet |
Matz, Julie Kessler, Pascal Bouchet, Jérôme Combes, Olivier Ramos, Oscar Henrique Pereira Barin, Francis Baty, Daniel Martin, Loïc Benichou, Serge Chames, Patrick Matz, Julie Kessler, Pascal Bouchet, Jérôme Combes, Olivier Ramos, Oscar Henrique Pereira Barin, Francis Baty, Daniel Martin, Loïc Benichou, Serge Chames, Patrick |
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author |
Matz, Julie Kessler, Pascal Bouchet, Jérôme Combes, Olivier Ramos, Oscar Henrique Pereira Barin, Francis Baty, Daniel Martin, Loïc Benichou, Serge Chames, Patrick |
spellingShingle |
Matz, Julie Kessler, Pascal Bouchet, Jérôme Combes, Olivier Ramos, Oscar Henrique Pereira Barin, Francis Baty, Daniel Martin, Loïc Benichou, Serge Chames, Patrick Journal of Virology Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 Virology Insect Science Immunology Microbiology |
author_sort |
matz, julie |
spelling |
Matz, Julie Kessler, Pascal Bouchet, Jérôme Combes, Olivier Ramos, Oscar Henrique Pereira Barin, Francis Baty, Daniel Martin, Loïc Benichou, Serge Chames, Patrick 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.00461-12 <jats:title>ABSTRACT</jats:title> <jats:p>Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, HIV-1 employs many strategies to evade humoral immune response toward these sensitive sites, including a carbohydrate shield, low accessibility to these buried cavities, and conformational masking. Using trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS, respectively). When analyzed as monomers or as homo- or heteromultimers, the best sdAb candidates could not only neutralize viruses carrying subtype B envelopes, corresponding to the Env molecule used for immunization and selection, but were also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G, CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers exhibited a broader neutralizing activity spectrum than the parental sdAb monomers. The extreme stability and high recombinant production yield combined with their broad neutralization capacity make these sdAbs new potential microbicide candidates for HIV-1 transmission prevention.</jats:p> Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 Journal of Virology |
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American Society for Microbiology, 2013 |
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American Society for Microbiology, 2013 |
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American Society for Microbiology |
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title |
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_unstemmed |
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_full |
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_fullStr |
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_full_unstemmed |
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_short |
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_sort |
straightforward selection of broadly neutralizing single-domain antibodies targeting the conserved cd4 and coreceptor binding sites of hiv-1 gp120 |
topic |
Virology Insect Science Immunology Microbiology |
url |
http://dx.doi.org/10.1128/jvi.00461-12 |
publishDate |
2013 |
physical |
1137-1149 |
description |
<jats:title>ABSTRACT</jats:title>
<jats:p>Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, HIV-1 employs many strategies to evade humoral immune response toward these sensitive sites, including a carbohydrate shield, low accessibility to these buried cavities, and conformational masking. Using trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS, respectively). When analyzed as monomers or as homo- or heteromultimers, the best sdAb candidates could not only neutralize viruses carrying subtype B envelopes, corresponding to the Env molecule used for immunization and selection, but were also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G, CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers exhibited a broader neutralizing activity spectrum than the parental sdAb monomers. The extreme stability and high recombinant production yield combined with their broad neutralization capacity make these sdAbs new potential microbicide candidates for HIV-1 transmission prevention.</jats:p> |
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author | Matz, Julie, Kessler, Pascal, Bouchet, Jérôme, Combes, Olivier, Ramos, Oscar Henrique Pereira, Barin, Francis, Baty, Daniel, Martin, Loïc, Benichou, Serge, Chames, Patrick |
author_facet | Matz, Julie, Kessler, Pascal, Bouchet, Jérôme, Combes, Olivier, Ramos, Oscar Henrique Pereira, Barin, Francis, Baty, Daniel, Martin, Loïc, Benichou, Serge, Chames, Patrick, Matz, Julie, Kessler, Pascal, Bouchet, Jérôme, Combes, Olivier, Ramos, Oscar Henrique Pereira, Barin, Francis, Baty, Daniel, Martin, Loïc, Benichou, Serge, Chames, Patrick |
author_sort | matz, julie |
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description | <jats:title>ABSTRACT</jats:title> <jats:p>Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, HIV-1 employs many strategies to evade humoral immune response toward these sensitive sites, including a carbohydrate shield, low accessibility to these buried cavities, and conformational masking. Using trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS, respectively). When analyzed as monomers or as homo- or heteromultimers, the best sdAb candidates could not only neutralize viruses carrying subtype B envelopes, corresponding to the Env molecule used for immunization and selection, but were also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G, CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers exhibited a broader neutralizing activity spectrum than the parental sdAb monomers. The extreme stability and high recombinant production yield combined with their broad neutralization capacity make these sdAbs new potential microbicide candidates for HIV-1 transmission prevention.</jats:p> |
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spelling | Matz, Julie Kessler, Pascal Bouchet, Jérôme Combes, Olivier Ramos, Oscar Henrique Pereira Barin, Francis Baty, Daniel Martin, Loïc Benichou, Serge Chames, Patrick 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.00461-12 <jats:title>ABSTRACT</jats:title> <jats:p>Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, HIV-1 employs many strategies to evade humoral immune response toward these sensitive sites, including a carbohydrate shield, low accessibility to these buried cavities, and conformational masking. Using trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS, respectively). When analyzed as monomers or as homo- or heteromultimers, the best sdAb candidates could not only neutralize viruses carrying subtype B envelopes, corresponding to the Env molecule used for immunization and selection, but were also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G, CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers exhibited a broader neutralizing activity spectrum than the parental sdAb monomers. The extreme stability and high recombinant production yield combined with their broad neutralization capacity make these sdAbs new potential microbicide candidates for HIV-1 transmission prevention.</jats:p> Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 Journal of Virology |
spellingShingle | Matz, Julie, Kessler, Pascal, Bouchet, Jérôme, Combes, Olivier, Ramos, Oscar Henrique Pereira, Barin, Francis, Baty, Daniel, Martin, Loïc, Benichou, Serge, Chames, Patrick, Journal of Virology, Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120, Virology, Insect Science, Immunology, Microbiology |
title | Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_full | Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_fullStr | Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_full_unstemmed | Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_short | Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
title_sort | straightforward selection of broadly neutralizing single-domain antibodies targeting the conserved cd4 and coreceptor binding sites of hiv-1 gp120 |
title_unstemmed | Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120 |
topic | Virology, Insect Science, Immunology, Microbiology |
url | http://dx.doi.org/10.1128/jvi.00461-12 |