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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033298&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849434483163398144 |
|---|---|
| author | Nika Strokappe Agnieszka Szynol Marlèn Aasa-Chapman Andrea Gorlani Anna Forsman Quigley David Lutje Hulsik Lei Chen Robin Weiss Hans de Haard Theo Verrips |
| author_facet | Nika Strokappe Agnieszka Szynol Marlèn Aasa-Chapman Andrea Gorlani Anna Forsman Quigley David Lutje Hulsik Lei Chen Robin Weiss Hans de Haard Theo Verrips |
| author_sort | Nika Strokappe |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-95c6cab2498e49dab1a65a266b6337cd |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-95c6cab2498e49dab1a65a266b6337cd2025-08-20T03:26:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3329810.1371/journal.pone.0033298Llama antibody fragments recognizing various epitopes of the CD4bs neutralize a broad range of HIV-1 subtypes A, B and C.Nika StrokappeAgnieszka SzynolMarlèn Aasa-ChapmanAndrea GorlaniAnna Forsman QuigleyDavid Lutje HulsikLei ChenRobin WeissHans de HaardTheo VerripsMany 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033298&type=printable |
| spellingShingle | Nika Strokappe Agnieszka Szynol Marlèn Aasa-Chapman Andrea Gorlani Anna Forsman Quigley David Lutje Hulsik Lei Chen Robin Weiss Hans de Haard Theo Verrips Llama antibody fragments recognizing various epitopes of the CD4bs neutralize a broad range of HIV-1 subtypes A, B and C. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033298&type=printable |
| work_keys_str_mv | AT nikastrokappe llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT agnieszkaszynol llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT marlenaasachapman llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT andreagorlani llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT annaforsmanquigley llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT davidlutjehulsik llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT leichen llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT robinweiss llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT hansdehaard llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc AT theoverrips llamaantibodyfragmentsrecognizingvariousepitopesofthecd4bsneutralizeabroadrangeofhiv1subtypesabandc |