Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing.
Although vaccines are important in preventing viral infections by inducing neutralizing antibodies (nAbs), HIV-1 has proven to be a difficult target and escapes humoral immunity through various mechanisms. We sought to test whether HIV-1 Env mimics may serve as immunogens.Using random peptide phage...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2597739?pdf=render |
| _version_ | 1819123472369975296 |
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| author | Michael Humbert Robert A Rasmussen Helena Ong Fabian M P Kaiser Shiu-Lok Hu Ruth M Ruprecht |
| author_facet | Michael Humbert Robert A Rasmussen Helena Ong Fabian M P Kaiser Shiu-Lok Hu Ruth M Ruprecht |
| author_sort | Michael Humbert |
| collection | DOAJ |
| description | Although vaccines are important in preventing viral infections by inducing neutralizing antibodies (nAbs), HIV-1 has proven to be a difficult target and escapes humoral immunity through various mechanisms. We sought to test whether HIV-1 Env mimics may serve as immunogens.Using random peptide phage display libraries, we identified the epitopes recognized by polyclonal antibodies of a rhesus monkey that had developed high-titer, broadly reactive nAbs after infection with a simian-human immunodeficiency virus (SHIV) encoding env of a recently transmitted HIV-1 clade C (HIV-C). Phage peptide inserts were analyzed for conformational and linear homology using computational analysis; some peptides mimicked various domains of the original HIV-C Env, such as conformational V3 loop epitopes and the conserved linear region of the gp120 C-terminus. Next, we devised a novel prime/boost strategy to test the immunogenicity of such phage-displayed peptides and primed mice only once with HIV-C gp160 DNA followed by boosting with mixtures of recombinant phages.This strategy, which was designed to focus the immune system on a few Env epitopes (immunofocusing), not only induced HIV-C gp160 binding antibodies and cross-clade nAbs, but also linked a conserved HIV Env region for the first time to the induction of nAbs: the C-terminus of gp120. The identification of conserved antigen mimics may lead to novel immunogens capable of inducing broadly reactive nAbs. |
| first_indexed | 2024-12-22T07:08:53Z |
| format | Article |
| id | doaj.art-64b889ddfcf948f2bbba16b20a7db961 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:08:53Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-64b889ddfcf948f2bbba16b20a7db9612022-12-21T18:34:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e393710.1371/journal.pone.0003937Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing.Michael HumbertRobert A RasmussenHelena OngFabian M P KaiserShiu-Lok HuRuth M RuprechtAlthough vaccines are important in preventing viral infections by inducing neutralizing antibodies (nAbs), HIV-1 has proven to be a difficult target and escapes humoral immunity through various mechanisms. We sought to test whether HIV-1 Env mimics may serve as immunogens.Using random peptide phage display libraries, we identified the epitopes recognized by polyclonal antibodies of a rhesus monkey that had developed high-titer, broadly reactive nAbs after infection with a simian-human immunodeficiency virus (SHIV) encoding env of a recently transmitted HIV-1 clade C (HIV-C). Phage peptide inserts were analyzed for conformational and linear homology using computational analysis; some peptides mimicked various domains of the original HIV-C Env, such as conformational V3 loop epitopes and the conserved linear region of the gp120 C-terminus. Next, we devised a novel prime/boost strategy to test the immunogenicity of such phage-displayed peptides and primed mice only once with HIV-C gp160 DNA followed by boosting with mixtures of recombinant phages.This strategy, which was designed to focus the immune system on a few Env epitopes (immunofocusing), not only induced HIV-C gp160 binding antibodies and cross-clade nAbs, but also linked a conserved HIV Env region for the first time to the induction of nAbs: the C-terminus of gp120. The identification of conserved antigen mimics may lead to novel immunogens capable of inducing broadly reactive nAbs.http://europepmc.org/articles/PMC2597739?pdf=render |
| spellingShingle | Michael Humbert Robert A Rasmussen Helena Ong Fabian M P Kaiser Shiu-Lok Hu Ruth M Ruprecht Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing. PLoS ONE |
| title | Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing. |
| title_full | Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing. |
| title_fullStr | Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing. |
| title_full_unstemmed | Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing. |
| title_short | Inducing cross-clade neutralizing antibodies against HIV-1 by immunofocusing. |
| title_sort | inducing cross clade neutralizing antibodies against hiv 1 by immunofocusing |
| url | http://europepmc.org/articles/PMC2597739?pdf=render |
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