Llama antibody fragments recognizing various epitopes of the CD4bs neutralize a broad range of HIV-1 subtypes A, B and C
| العنوان: | Llama antibody fragments recognizing various epitopes of the CD4bs neutralize a broad range of HIV-1 subtypes A, B and C |
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| المؤلفون: | Andrea Gorlani, David Lutje Hulsik, Anna Forsman Quigley, Lei Chen, Agnieszka Szynol, Marlén M. I. Aasa-Chapman, Nika M. Strokappe, Robin A. Weiss, Hans de Haard, Theo Verrips |
| المساهمون: | Chen, Zhiwei |
| المصدر: | PLoS ONE, Vol 7, Iss 3, p e33298 (2012) PloS one, vol 7, iss 3 PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Viral Diseases, Phage display, Immunoglobulin Variable Region, Sequence Homology, lcsh:Medicine, Complementarity determining region, HIV Envelope Protein gp120, HIV Antibodies, Biochemistry, Epitope, Neutralization, env Gene Products, law.invention, Epitopes, Competitive, law, Site-Directed, lcsh:Science, Neutralizing, Multidisciplinary, biology, env Gene Products, Human Immunodeficiency Virus, New World, Amino Acid, Infectious Diseases, CD4 Antigens, Recombinant DNA, HIV/AIDS, Medicine, Antibody, Infection, Immunoglobulin Heavy Chains, Camelids, New World, Human Immunodeficiency Virus, Research Article, General Science & Technology, Immunology, Molecular Sequence Data, Cross Reactions, In Vitro Techniques, Binding, Competitive, Microbiology, Antibodies, Viral envelope, Neutralization Tests, Virology, Animals, Humans, Amino Acid Sequence, Antigens, Biology, Sequence Homology, Amino Acid, Prevention, lcsh:R, Immunity, Proteins, Binding, Antibodies, Neutralizing, Complementarity Determining Regions, Molecular biology, CD4, Good Health and Well Being, Amino Acid Substitution, Mutagenesis, Camelids, Mutagenesis, Site-Directed, HIV-1, biology.protein, Immunoglobulin heavy chain, Immunization, lcsh:Q |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf42588a745fedf0732b00df6b1433ca http://europepmc.org/articles/PMC3305327?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bf42588a745fedf0732b00df6b1433ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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