Design and pre-clinical evaluation of a universal HIV-1 vaccine.
<h4>Background</h4>One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.<h4>Methodology and findings</h4>To address the HIV-1 variation, we designed...
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| Format: | Article |
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Public Library of Science (PLoS)
2007-10-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000984&type=printable |
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| author | Sven Létourneau Eung-Jun Im Tumelo Mashishi Choechoe Brereton Anne Bridgeman Hongbing Yang Lucy Dorrell Tao Dong Bette Korber Andrew J McMichael Tomás Hanke |
| author_facet | Sven Létourneau Eung-Jun Im Tumelo Mashishi Choechoe Brereton Anne Bridgeman Hongbing Yang Lucy Dorrell Tao Dong Bette Korber Andrew J McMichael Tomás Hanke |
| author_sort | Sven Létourneau |
| collection | DOAJ |
| description | <h4>Background</h4>One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.<h4>Methodology and findings</h4>To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection.<h4>Significance</h4>Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity. |
| format | Article |
| id | doaj-art-0d11f9c277e444f483ae1fa7a1fd0edf |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2007-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-0d11f9c277e444f483ae1fa7a1fd0edf2025-08-20T02:00:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-10-01210e98410.1371/journal.pone.0000984Design and pre-clinical evaluation of a universal HIV-1 vaccine.Sven LétourneauEung-Jun ImTumelo MashishiChoechoe BreretonAnne BridgemanHongbing YangLucy DorrellTao DongBette KorberAndrew J McMichaelTomás Hanke<h4>Background</h4>One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.<h4>Methodology and findings</h4>To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection.<h4>Significance</h4>Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000984&type=printable |
| spellingShingle | Sven Létourneau Eung-Jun Im Tumelo Mashishi Choechoe Brereton Anne Bridgeman Hongbing Yang Lucy Dorrell Tao Dong Bette Korber Andrew J McMichael Tomás Hanke Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS ONE |
| title | Design and pre-clinical evaluation of a universal HIV-1 vaccine. |
| title_full | Design and pre-clinical evaluation of a universal HIV-1 vaccine. |
| title_fullStr | Design and pre-clinical evaluation of a universal HIV-1 vaccine. |
| title_full_unstemmed | Design and pre-clinical evaluation of a universal HIV-1 vaccine. |
| title_short | Design and pre-clinical evaluation of a universal HIV-1 vaccine. |
| title_sort | design and pre clinical evaluation of a universal hiv 1 vaccine |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000984&type=printable |
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