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Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C

Many of the neutralising antibodies, isolated to date, display limited activities against the globally most prevalent HIV-1 subtypes A and C. Therefore, those subtypes are considered to be an important target for antibody-based therapy. Variable domains of llama heavy chain antibodies (VHH) have som...

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Autores principales: Strokappe, Nika, Szynol, Agnieszka, Aasa-Chapman, Marlèn, Gorlani, Andrea, Forsman Quigley, Anna, Hulsik, David Lutje, Chen, Lei, Weiss, Robin, de Haard, Hans, Verrips, Theo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305327/
https://www.ncbi.nlm.nih.gov/pubmed/22438910
http://dx.doi.org/10.1371/journal.pone.0033298
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author Strokappe, Nika
Szynol, Agnieszka
Aasa-Chapman, Marlèn
Gorlani, Andrea
Forsman Quigley, Anna
Hulsik, David Lutje
Chen, Lei
Weiss, Robin
de Haard, Hans
Verrips, Theo
author_facet Strokappe, Nika
Szynol, Agnieszka
Aasa-Chapman, Marlèn
Gorlani, Andrea
Forsman Quigley, Anna
Hulsik, David Lutje
Chen, Lei
Weiss, Robin
de Haard, Hans
Verrips, Theo
author_sort Strokappe, Nika
collection PubMed
description Many of the neutralising antibodies, isolated to date, display limited activities against the globally most prevalent HIV-1 subtypes A and C. Therefore, those subtypes are considered to be an important target for antibody-based therapy. Variable domains of llama heavy chain antibodies (VHH) have some superior properties compared with classical antibodies. Therefore we describe the application of trimeric forms of envelope proteins (Env), derived from HIV-1 of subtype A and B/C, for a prolonged immunization of two llamas. A panel of VHH, which interfere with CD4 binding to HIV-1 Env were selected with use of panning. The results of binding and competition assays to various Env, including a variant with a stabilized CD4-binding state (gp120(Ds2)), cross-competition experiments, maturation analysis and neutralisation assays, enabled us to classify the selected VHH into three groups. The VHH of group I were efficient mainly against viruses of subtype A, C and B′/C. The VHH of group II resemble the broadly neutralising antibody (bnmAb) b12, neutralizing mainly subtype B and C viruses, however some had a broader neutralisation profile. A representative of the third group, 2E7, had an even higher neutralization breadth, neutralizing 21 out of the 26 tested strains belonging to the A, A/G, B, B/C and C subtypes. To evaluate the contribution of certain amino acids to the potency of the VHH a small set of the mutants were constructed. Surprisingly this yielded one mutant with slightly improved neutralisation potency against 92UG37.A9 (subtype A) and 96ZM651.02 (subtype C). These findings and the well-known stability of VHH indicate the potential application of these VHH as anti-HIV-1 microbicides.
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spelling pubmed-33053272012-03-21 Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C Strokappe, Nika Szynol, Agnieszka Aasa-Chapman, Marlèn Gorlani, Andrea Forsman Quigley, Anna Hulsik, David Lutje Chen, Lei Weiss, Robin de Haard, Hans Verrips, Theo PLoS One Research Article Many of the neutralising antibodies, isolated to date, display limited activities against the globally most prevalent HIV-1 subtypes A and C. Therefore, those subtypes are considered to be an important target for antibody-based therapy. Variable domains of llama heavy chain antibodies (VHH) have some superior properties compared with classical antibodies. Therefore we describe the application of trimeric forms of envelope proteins (Env), derived from HIV-1 of subtype A and B/C, for a prolonged immunization of two llamas. A panel of VHH, which interfere with CD4 binding to HIV-1 Env were selected with use of panning. The results of binding and competition assays to various Env, including a variant with a stabilized CD4-binding state (gp120(Ds2)), cross-competition experiments, maturation analysis and neutralisation assays, enabled us to classify the selected VHH into three groups. The VHH of group I were efficient mainly against viruses of subtype A, C and B′/C. The VHH of group II resemble the broadly neutralising antibody (bnmAb) b12, neutralizing mainly subtype B and C viruses, however some had a broader neutralisation profile. A representative of the third group, 2E7, had an even higher neutralization breadth, neutralizing 21 out of the 26 tested strains belonging to the A, A/G, B, B/C and C subtypes. To evaluate the contribution of certain amino acids to the potency of the VHH a small set of the mutants were constructed. Surprisingly this yielded one mutant with slightly improved neutralisation potency against 92UG37.A9 (subtype A) and 96ZM651.02 (subtype C). These findings and the well-known stability of VHH indicate the potential application of these VHH as anti-HIV-1 microbicides. Public Library of Science 2012-03-15 /pmc/articles/PMC3305327/ /pubmed/22438910 http://dx.doi.org/10.1371/journal.pone.0033298 Text en Strokappe et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Strokappe, Nika
Szynol, Agnieszka
Aasa-Chapman, Marlèn
Gorlani, Andrea
Forsman Quigley, Anna
Hulsik, David Lutje
Chen, Lei
Weiss, Robin
de Haard, Hans
Verrips, Theo
Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C
title Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C
title_full Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C
title_fullStr Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C
title_full_unstemmed Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C
title_short Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C
title_sort llama antibody fragments recognizing various epitopes of the cd4bs neutralize a broad range of hiv-1 subtypes a, b and c
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305327/
https://www.ncbi.nlm.nih.gov/pubmed/22438910
http://dx.doi.org/10.1371/journal.pone.0033298
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